The role of chemokines and their receptors in angiogenesis

Cellular and Molecular Life Sciences - Tập 68 - Trang 2811-2830 - 2011
Friedemann Kiefer1, Arndt F. Siekmann1
1Max Planck Institute for Molecular Biomedicine, Muenster, Germany

Tóm tắt

Chemokines are a vertebrate-specific group of small molecules that regulate cell migration and behaviour in diverse contexts. So far, around 50 chemokines have been identified in humans, which bind to 18 different chemokine receptors. These are members of the seven-transmembrane receptor family. Initially, chemokines were identified as modulators of the immune response. Subsequently, they were also shown to regulate cell migration during embryonic development. Here, we discuss the influence of chemokines and their receptors on angiogenesis, or the formation of new blood vessels. We highlight recent advances in our understanding of how chemokine signalling might directly influence endothelial cell migration. We furthermore examine the contributions of chemokine signalling in immune cells during this process. Finally, we explore possible implications for disease settings, such as chronic inflammation and tumour progression.

Tài liệu tham khảo

Risau W (1997) Mechanisms of angiogenesis. Nature 386(6626):671–674 Olsson AK, Dimberg A, Kreuger J, Claesson-Welsh L (2006) VEGF receptor signalling – in control of vascular function. Nat Rev Mol Cell Biol 7(5):359–371 Carmeliet P, Ferreira V, Breier G, Pollefeyt S, Kieckens L, Gertsenstein M, Fahrig M, Vandenhoeck A, Harpal K, Eberhardt C, Declercq C, Pawling J, Moons L, Collen D, Risau W, Nagy A (1996) Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature 380(6573):435–439 Ferrara N, Carver-Moore K, Chen H, Dowd M, Lu L, O’Shea KS, Powell-Braxton L, Hillan KJ, Moore MW (1996) Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene. Nature 380(6573):439–442 Nasevicius A, Larson J, Ekker SC (2000) Distinct requirements for zebrafish angiogenesis revealed by a VEGF-A morphant. Yeast 17(4):294–301 Gridley T (2010) Notch signaling in the vasculature. Curr Top Dev Biol 92:277–309 le Noble F, Fleury V, Pries A, Corvol P, Eichmann A, Reneman RS (2005) Control of arterial branching morphogenesis in embryogenesis: go with the flow. Cardiovasc Res 65(3):619–628 Germain S, Monnot C, Muller L, Eichmann A (2010) Hypoxia-driven angiogenesis: role of tip cells and extracellular matrix scaffolding. Curr Opin Hematol 17(3):245–251 Carmeliet P (2003) Angiogenesis in health and disease. Nat Med 9(6):653–660 Jenab-Wolcott J, Giantonio BJ (2009) Bevacizumab: current indications and future development for management of solid tumors. Expert Opin Biol Ther 9(4):507–517 Ozkiris A (2010) Anti-VEGF agents for age-related macular degeneration. Expert Opin Ther Pat 20(1):103–118 Fantin A, Vieira JM, Gestri G, Denti L, Schwarz Q, Prykhozhij S, Peri F, Wilson SW, Ruhrberg C (2010) Tissue macrophages act as cellular chaperones for vascular anastomosis downstream of VEGF-mediated endothelial tip cell induction. Blood 116(5):829–840 Adamson R (2009) Role of macrophages in normal wound healing: an overview. J Wound Care 18(8):349–351 Hall K, Ran S (2010) Regulation of tumor angiogenesis by the local environment. Front Biosci 15:195–212 Bohmer R, Neuhaus B, Buhren S, Zhang D, Stehling M, Bock B, Kiefer F (2010) Regulation of developmental lymphangiogenesis by Syk(+) leukocytes. Dev Cell 18(3):437–449 Gordon EJ, Rao S, Pollard JW, Nutt SL, Lang RA, Harvey NL (2010) Macrophages define dermal lymphatic vessel calibre during development by regulating lymphatic endothelial cell proliferation. Development 137(22):3899–3910 Zlotnik A, Yoshie O (2000) Chemokines: a new classification system and their role in immunity. Immunity 12(2):121–127 Lazennec G, Richmond A (2010) Chemokines and chemokine receptors: new insights into cancer-related inflammation. Trends Mol Med 16(3):133–144 Thelen M, Stein JV (2008) How chemokines invite leukocytes to dance. Nat Immunol 9(9):953–959 Strieter RM, Burdick MD, Gomperts BN, Belperio JA, Keane MP (2005) CXC chemokines in angiogenesis. Cytokine Growth Factor Rev 16(6):593–609 Addison CL, Daniel TO, Burdick MD, Liu H, Ehlert JE, Xue YY, Buechi L, Walz A, Richmond A, Strieter RM (2000) The CXC chemokine receptor 2, CXCR2, is the putative receptor for ELR+ CXC chemokine-induced angiogenic activity. J Immunol 165(9):5269–5277 Wolf M, Delgado MB, Jones SA, Dewald B, Clark-Lewis I, Baggiolini M (1998) Granulocyte chemotactic protein 2 acts via both IL-8 receptors, CXCR1 and CXCR2. Eur J Immunol 28(1):164–170 Salcedo R, Resau JH, Halverson D, Hudson EA, Dambach M, Powell D, Wasserman K, Oppenheim JJ (2000) Differential expression and responsiveness of chemokine receptors (CXCR1-3) by human microvascular endothelial cells and umbilical vein endothelial cells. FASEB J 14(13):2055–2064 Schraufstatter IU, Chung J, Burger M (2001) IL-8 activates endothelial cell CXCR1 and CXCR2 through Rho and Rac signaling pathways. Am J Physiol Lung Cell Mol Physiol 280(6):L1094–L1103 Heidemann J, Ogawa H, Dwinell MB, Rafiee P, Maaser C, Gockel HR, Otterson MF, Ota DM, Lugering N, Domschke W, Binion DG (2003) Angiogenic effects of interleukin 8 (CXCL8) in human intestinal microvascular endothelial cells are mediated by CXCR2. J Biol Chem 278(10):8508–8515 Devalaraja RM, Nanney LB, Du J, Qian Q, Yu Y, Devalaraja MN, Richmond A (2000) Delayed wound healing in CXCR2 knockout mice. J Invest Dermatol 115(2):234–244 Cacalano G, Lee J, Kikly K, Ryan AM, Pitts-Meek S, Hultgren B, Wood WI, Moore MW (1994) Neutrophil and B cell expansion in mice that lack the murine IL-8 receptor homolog. Science 265(5172):682–684 Salcedo R, Wasserman K, Young HA, Grimm MC, Howard OM, Anver MR, Kleinman HK, Murphy WJ, Oppenheim JJ (1999) Vascular endothelial growth factor and basic fibroblast growth factor induce expression of CXCR4 on human endothelial cells: in vivo neovascularization induced by stromal-derived factor-1alpha. Am J Pathol 154(4):1125–1135 Burns JM, Summers BC, Wang Y, Melikian A, Berahovich R, Miao Z, Penfold ME, Sunshine MJ, Littman DR, Kuo CJ, Wei K, McMaster BE, Wright K, Howard MC, Schall TJ (2006) A novel chemokine receptor for SDF-1 and I-TAC involved in cell survival, cell adhesion, and tumor development. J Exp Med 203(9):2201–2213 Miao Z, Luker KE, Summers BC, Berahovich R, Bhojani MS, Rehemtulla A, Kleer CG, Essner JJ, Nasevicius A, Luker GD, Howard MC, Schall TJ (2007) CXCR7 (RDC1) promotes breast and lung tumor growth in vivo and is expressed on tumor-associated vasculature. Proc Natl Acad Sci U S A 104(40):15735–15740 Guyon A, Nahon JL (2007) Multiple actions of the chemokine stromal cell-derived factor-1alpha on neuronal activity. J Mol Endocrinol 38(3):365–376 Rajagopal S, Kim J, Ahn S, Craig S, Lam CM, Gerard NP, Gerard C, Lefkowitz RJ (2010) Beta-arrestin- but not G protein-mediated signaling by the “decoy” receptor CXCR7. Proc Natl Acad Sci U S A 107(2):628–632 Levoye A, Balabanian K, Baleux F, Bachelerie F, Lagane B (2009) CXCR7 heterodimerizes with CXCR4 and regulates CXCL12-mediated G protein signaling. Blood 113(24):6085–6093 Sierro F, Biben C, Martinez-Munoz L, Mellado M, Ransohoff RM, Li M, Woehl B, Leung H, Groom J, Batten M, Harvey RP, Martinez AC, Mackay CR, Mackay F (2007) Disrupted cardiac development but normal hematopoiesis in mice deficient in the second CXCL12/SDF-1 receptor, CXCR7. Proc Natl Acad Sci U S A 104(37):14759–14764 Boldajipour B, Mahabaleshwar H, Kardash E, Reichman-Fried M, Blaser H, Minina S, Wilson D, Xu Q, Raz E (2008) Control of chemokine-guided cell migration by ligand sequestration. Cell 132(3):463–473 Dambly-Chaudiere C, Cubedo N, Ghysen A (2007) Control of cell migration in the development of the posterior lateral line: antagonistic interactions between the chemokine receptors CXCR4 and CXCR7/RDC1. BMC Dev Biol 7:23 Maione TE, Gray GS, Petro J, Hunt AJ, Donner AL, Bauer SI, Carson HF, Sharpe RJ (1990) Inhibition of angiogenesis by recombinant human platelet factor-4 and related peptides. Science 247(4938):77–79 Taylor S, Folkman J (1982) Protamine is an inhibitor of angiogenesis. Nature 297(5864):307–312 Weber C (2005) Platelets and chemokines in atherosclerosis: partners in crime. Circ Res 96(6):612–616 Flad HD, Brandt E (2010) Platelet-derived chemokines: pathophysiology and therapeutic aspects. Cell Mol Life Sci 67(14):2363–2386 Struyf S, Burdick MD, Proost P, Van Damme J, Strieter RM (2004) Platelets release CXCL4L1, a nonallelic variant of the chemokine platelet factor-4/CXCL4 and potent inhibitor of angiogenesis. Circ Res 95(9):855–857 Gupta SK, Singh JP (1994) Inhibition of endothelial cell proliferation by platelet factor-4 involves a unique action on S phase progression. J Cell Biol 127(4):1121–1127 Sato Y, Abe M, Takaki R (1990) Platelet factor 4 blocks the binding of basic fibroblast growth factor to the receptor and inhibits the spontaneous migration of vascular endothelial cells. Biochem Biophys Res Commun 172(2):595–600 Gengrinovitch S, Greenberg SM, Cohen T, Gitay-Goren H, Rockwell P, Maione TE, Levi BZ, Neufeld G (1995) Platelet factor-4 inhibits the mitogenic activity of VEGF121 and VEGF165 using several concurrent mechanisms. J Biol Chem 270(25):15059–15065 Perollet C, Han ZC, Savona C, Caen JP, Bikfalvi A (1998) Platelet factor 4 modulates fibroblast growth factor 2 (FGF-2) activity and inhibits FGF-2 dimerization. Blood 91(9):3289–3299 Jouan V, Canron X, Alemany M, Caen JP, Quentin G, Plouet J, Bikfalvi A (1999) Inhibition of in vitro angiogenesis by platelet factor-4-derived peptides and mechanism of action. Blood 94(3):984–993 Ferrara N (2010) Binding to the extracellular matrix and proteolytic processing: two key mechanisms regulating vascular endothelial growth factor action. Mol Biol Cell 21(5):687–690 Keeley EC, Mehrad B, Strieter RM (2008) Chemokines as mediators of neovascularization. Arterioscler Thromb Vasc Biol 28(11):1928–1936 Loetscher M, Gerber B, Loetscher P, Jones SA, Piali L, Clark-Lewis I, Baggiolini M, Moser B (1996) Chemokine receptor specific for IP10 and mig: structure, function, and expression in activated T-lymphocytes. J Exp Med 184(3):963–969 Moser B, Loetscher P (2001) Lymphocyte traffic control by chemokines. Nat Immunol 2(2):123–128 Lasagni L, Francalanci M, Annunziato F, Lazzeri E, Giannini S, Cosmi L, Sagrinati C, Mazzinghi B, Orlando C, Maggi E, Marra F, Romagnani S, Serio M, Romagnani P (2003) An alternatively spliced variant of CXCR3 mediates the inhibition of endothelial cell growth induced by IP-10, Mig, and I-TAC, and acts as functional receptor for platelet factor 4. J Exp Med 197(11):1537–1549 Romagnani P, Annunziato F, Lasagni L, Lazzeri E, Beltrame C, Francalanci M, Uguccioni M, Galli G, Cosmi L, Maurenzig L, Baggiolini M, Maggi E, Romagnani S, Serio M (2001) Cell cycle-dependent expression of CXC chemokine receptor 3 by endothelial cells mediates angiostatic activity. J Clin Invest 107(1):53–63 Yang J, Richmond A (2004) The angiostatic activity of interferon-inducible protein-10/CXCL10 in human melanoma depends on binding to CXCR3 but not to glycosaminoglycan. Mol Ther 9(6):846–855 Campanella GS, Colvin RA, Luster AD (2010) CXCL10 can inhibit endothelial cell proliferation independently of CXCR3. PLoS One 5(9):e12700 Mellado M, Rodriguez-Frade JM, Manes S, Martinez A (2001) Chemokine signaling and functional responses: the role of receptor dimerization and TK pathway activation. Annu Rev Immunol 19:397–421 Hanyaloglu AC, von Zastrow M (2008) Regulation of GPCRs by endocytic membrane trafficking and its potential implications. Annu Rev Pharmacol Toxicol 48:537–568 Mariani M, Lang R, Binda E, Panina-Bordignon P, D’Ambrosio D (2004) Dominance of CCL22 over CCL17 in induction of chemokine receptor CCR4 desensitization and internalization on human Th2 cells. Eur J Immunol 34(1):231–240 Mueller A, Strange PG (2004) Mechanisms of internalization and recycling of the chemokine receptor, CCR5. Eur J Biochem 271(2):243–252 Zidar DA, Violin JD, Whalen EJ, Lefkowitz RJ (2009) Selective engagement of G protein coupled receptor kinases (GRKs) encodes distinct functions of biased ligands. Proc Natl Acad Sci U S A 106(24):9649–9654 Signoret N, Pelchen-Matthews A, Mack M, Proudfoot AE, Marsh M (2000) Endocytosis and recycling of the HIV coreceptor CCR5. J Cell Biol 151(6):1281–1294 Zimmermann N, Conkright JJ, Rothenberg ME (1999) CC chemokine receptor-3 undergoes prolonged ligand-induced internalization. J Biol Chem 274(18):12611–12618 Elsner J, Mack M, Bruhl H, Dulkys Y, Kimmig D, Simmons G, Clapham PR, Schlondorff D, Kapp A, Wells TN, Proudfoot AE (2000) Differential activation of CC chemokine receptors by AOP-RANTES. J Biol Chem 275(11):7787–7794 Sorkin A, von Zastrow M (2009) Endocytosis and signalling: intertwining molecular networks. Nat Rev Mol Cell Biol 10(9):609–622 Borroni EM, Mantovani A, Locati M, Bonecchi R (2010) Chemokine receptors intracellular trafficking. Pharmacol Ther 127(1):1–8 Rubin JB (2009) Chemokine signaling in cancer: one hump or two? Semin Cancer Biol 19(2):116–122 Ward SG (2006) T lymphocytes on the move: chemokines, PI 3-kinase and beyond. Trends Immunol 27(2):80–87 Vanhaesebroeck B, Ali K, Bilancio A, Geering B, Foukas LC (2005) Signalling by PI3 K isoforms: insights from gene-targeted mice. Trends Biochem Sci 30(4):194–204 Hirsch E, Katanaev VL, Garlanda C, Azzolino O, Pirola L, Silengo L, Sozzani S, Mantovani A, Altruda F, Wymann MP (2000) Central role for G protein-coupled phosphoinositide 3-kinase gamma in inflammation. Science 287(5455):1049–1053 Cronshaw DG, Owen C, Brown Z, Ward SG (2004) Activation of phosphoinositide 3-kinases by the CCR4 ligand macrophage-derived chemokine is a dispensable signal for T lymphocyte chemotaxis. J Immunol 172(12):7761–7770 Curnock AP, Sotsios Y, Wright KL, Ward SG (2003) Optimal chemotactic responses of leukemic T cells to stromal cell-derived factor-1 requires the activation of both class IA and IB phosphoinositide 3-kinases. J Immunol 170(8):4021–4030 Merlot S, Firtel RA (2003) Leading the way: directional sensing through phosphatidylinositol 3-kinase and other signaling pathways. J Cell Sci 116(Pt 17):3471–3478 Barbero S, Bonavia R, Bajetto A, Porcile C, Pirani P, Ravetti JL, Zona GL, Spaziante R, Florio T, Schettini G (2003) Stromal cell-derived factor 1alpha stimulates human glioblastoma cell growth through the activation of both extracellular signal-regulated kinases 1/2 and Akt. Cancer Res 63(8):1969–1974 Suzuki Y, Rahman M, Mitsuya H (2001) Diverse transcriptional response of CD4(+) T cells to stromal cell-derived factor (SDF)-1: cell survival promotion and priming effects of SDF-1 on CD4(+) T cells. J Immunol 167(6):3064–3073 McGrath KE, Koniski AD, Maltby KM, McGann JK, Palis J (1999) Embryonic expression and function of the chemokine SDF-1 and its receptor, CXCR4. Dev Biol 213(2):442–456 Chong SW, Emelyanov A, Gong Z, Korzh V (2001) Expression pattern of two zebrafish genes, cxcr4a and cxcr4b. Mech Dev 109(2):347–354 Siekmann AF, Standley C, Fogarty KE, Wolfe SA, Lawson ND (2009) Chemokine signaling guides regional patterning of the first embryonic artery. Genes Dev 23(19):2272–2277 Tachibana K, Hirota S, Iizasa H, Yoshida H, Kawabata K, Kataoka Y, Kitamura Y, Matsushima K, Yoshida N, Nishikawa S, Kishimoto T, Nagasawa T (1998) The chemokine receptor CXCR4 is essential for vascularization of the gastrointestinal tract. Nature 393(6685):591–594 Ara T, Tokoyoda K, Okamoto R, Koni PA, Nagasawa T (2005) The role of CXCL12 in the organ-specific process of artery formation. Blood 105(8):3155–3161 Takabatake Y, Sugiyama T, Kohara H, Matsusaka T, Kurihara H, Koni PA, Nagasawa Y, Hamano T, Matsui I, Kawada N, Imai E, Nagasawa T, Rakugi H, Isaka Y (2009) The CXCL12 (SDF-1)/CXCR4 axis is essential for the development of renal vasculature. J Am Soc Nephrol 20(8):1714–1723 Nagasawa T, Hirota S, Tachibana K, Takakura N, Nishikawa S, Kitamura Y, Yoshida N, Kikutani H, Kishimoto T (1996) Defects of B-cell lymphopoiesis and bone-marrow myelopoiesis in mice lacking the CXC chemokine PBSF/SDF-1. Nature 382(6592):635–638 Gerrits H, van Ingen Schenau DS, Bakker NE, van Disseldorp AJ, Strik A, Hermens LS, Koenen TB, Krajnc-Franken MA, Gossen JA (2008) Early postnatal lethality and cardiovascular defects in CXCR7-deficient mice. Genesis 46(5):235–245 Gridley T (2007) Notch signaling in vascular development and physiology. Development 134(15):2709–2718 Strasser GA, Kaminker JS, Tessier-Lavigne M (2010) Microarray analysis of retinal endothelial tip cells identifies CXCR4 as a mediator of tip cell morphology and branching. Blood 115(24):5102–5110 Kubota Y, Takubo K, Shimizu T, Ohno H, Kishi K, Shibuya M, Saya H, Suda T (2009) M-CSF inhibition selectively targets pathological angiogenesis and lymphangiogenesis. J Exp Med 206(5):1089–1102 Siekmann AF, Covassin L, Lawson ND (2008) Modulation of VEGF signalling output by the Notch pathway. Bioessays 30(4):303–313 Phng LK, Gerhardt H (2009) Angiogenesis: a team effort coordinated by notch. Dev Cell 16(2):196–208 Williams CK, Segarra M, Sierra Mde L, Sainson RC, Tosato G, Harris AL (2008) Regulation of CXCR4 by the Notch ligand delta-like 4 in endothelial cells. Cancer Res 68(6):1889–1895 Packham IM, Gray C, Heath PR, Hellewell PG, Ingham PW, Crossman DC, Milo M, Chico TJ (2009) Microarray profiling reveals CXCR4a is downregulated by blood flow in vivo and mediates collateral formation in zebrafish embryos. Physiol Genomics 38(3):319–327 Melchionna R, Porcelli D, Mangoni A, Carlini D, Liuzzo G, Spinetti G, Antonini A, Capogrossi MC, Napolitano M (2005) Laminar shear stress inhibits CXCR4 expression on endothelial cells: functional consequences for atherogenesis. FASEB J 19(6):629–631 Tammela T, Alitalo K (2010) Lymphangiogenesis: molecular mechanisms and future promise. Cell 140(4):460–476 Oliver G (2004) Lymphatic vasculature development. Nat Rev Immunol 4(1):35–45 Karkkainen MJ, Haiko P, Sainio K, Partanen J, Taipale J, Petrova TV, Jeltsch M, Jackson DG, Talikka M, Rauvala H, Betsholtz C, Alitalo K (2004) Vascular endothelial growth factor C is required for sprouting of the first lymphatic vessels from embryonic veins. Nat Immunol 5(1):74–80 Bussmann J, Bos FL, Urasaki A, Kawakami K, Duckers HJ, Schulte-Merker S (2010) Arteries provide essential guidance cues for lymphatic endothelial cells in the zebrafish trunk. Development 137(16):2653–2657 Bertozzi CC, Schmaier AA, Mericko P, Hess PR, Zou Z, Chen M, Chen CY, Xu B, Lu MM, Zhou D, Sebzda E, Santore MT, Merianos DJ, Stadtfeld M, Flake AW, Graf T, Skoda R, Maltzman JS, Koretzky GA, Kahn ML (2010) Platelets regulate lymphatic vascular development through CLEC-2-SLP-76 signaling. Blood 116(4):661–670 Carramolino L, Fuentes J, Garcia-Andres C, Azcoitia V, Riethmacher D, Torres M (2010) Platelets play an essential role in separating the blood and lymphatic vasculatures during embryonic angiogenesis. Circ Res 106(7):1197–1201 Fu J, Gerhardt H, McDaniel JM, Xia B, Liu X, Ivanciu L, Ny A, Hermans K, Silasi-Mansat R, McGee S, Nye E, Ju T, Ramirez MI, Carmeliet P, Cummings RD, Lupu F, Xia L (2008) Endothelial cell O-glycan deficiency causes blood/lymphatic misconnections and consequent fatty liver disease in mice. J Clin Invest 118(11):3725–3737 Suzuki-Inoue K, Inoue O, Ding G, Nishimura S, Hokamura K, Eto K, Kashiwagi H, Tomiyama Y, Yatomi Y, Umemura K, Shin Y, Hirashima M, Ozaki Y (2010) Essential in vivo roles of the C-type lectin receptor CLEC-2: embryonic/neonatal lethality of CLEC-2-deficient mice by blood/lymphatic misconnections and impaired thrombus formation of CLEC-2-deficient platelets. J Biol Chem 285(32):24494–24507 Uhrin P, Zaujec J, Breuss JM, Olcaydu D, Chrenek P, Stockinger H, Fuertbauer E, Moser M, Haiko P, Fassler R, Alitalo K, Binder BR, Kerjaschki D (2010) Novel function for blood platelets and podoplanin in developmental separation of blood and lymphatic circulation. Blood 115(19):3997–4005 Abtahian F, Guerriero A, Sebzda E, Lu MM, Zhou R, Mocsai A, Myers EE, Huang B, Jackson DG, Ferrari VA, Tybulewicz V, Lowell CA, Lepore JJ, Koretzky GA, Kahn ML (2003) Regulation of blood and lymphatic vascular separation by signaling proteins SLP-76 and Syk. Science 299(5604):247–251 Turnbull IR, Colonna M (2007) Activating and inhibitory functions of DAP12. Nat Rev Immunol 7(2):155–161 Adams RH, Alitalo K (2007) Molecular regulation of angiogenesis and lymphangiogenesis. Nat Rev Mol Cell Biol 8(6):464–478 Mebius RE, Miyamoto T, Christensen J, Domen J, Cupedo T, Weissman IL, Akashi K (2001) The fetal liver counterpart of adult common lymphoid progenitors gives rise to all lymphoid lineages, CD45+ CD4+ CD3− cells, as well as macrophages. J Immunol 166(11):6593–6601 Kim D, Mebius RE, MacMicking JD, Jung S, Cupedo T, Castellanos Y, Rho J, Wong BR, Josien R, Kim N, Rennert PD, Choi Y (2000) Regulation of peripheral lymph node genesis by the tumor necrosis factor family member TRANCE. J Exp Med 192(10):1467–1478 Sun Z, Unutmaz D, Zou YR, Sunshine MJ, Pierani A, Brenner-Morton S, Mebius RE, Littman DR (2000) Requirement for RORgamma in thymocyte survival and lymphoid organ development. Science 288(5475):2369–2373 van de Pavert SA, Olivier BJ, Goverse G, Vondenhoff MF, Greuter M, Beke P, Kusser K, Hopken UE, Lipp M, Niederreither K, Blomhoff R, Sitnik K, Agace WW, Randall TD, de Jonge WJ, Mebius RE (2009) Chemokine CXCL13 is essential for lymph node initiation and is induced by retinoic acid and neuronal stimulation. Nat Immunol 10(11):1193–1199 Luther SA, Ansel KM, Cyster JG (2003) Overlapping roles of CXCL13, interleukin 7 receptor alpha, and CCR7 ligands in lymph node development. J Exp Med 197(9):1191–1198 Finke D, Acha-Orbea H, Mattis A, Lipp M, Kraehenbuhl J (2002) CD4+ CD3− cells induce Peyer’s patch development: role of alpha4beta1 integrin activation by CXCR5. Immunity 17(3):363–373 Drayton DL, Liao S, Mounzer RH, Ruddle NH (2006) Lymphoid organ development: from ontogeny to neogenesis. Nat Immunol 7(4):344–353 Rennert PD, James D, Mackay F, Browning JL, Hochman PS (1998) Lymph node genesis is induced by signaling through the lymphotoxin beta receptor. Immunity 9(1):71–79 Honda K, Nakano H, Yoshida H, Nishikawa S, Rennert P, Ikuta K, Tamechika M, Yamaguchi K, Fukumoto T, Chiba T, Nishikawa SI (2001) Molecular basis for hematopoietic/mesenchymal interaction during initiation of Peyer’s patch organogenesis. J Exp Med 193(5):621–630 Cupedo T, Mebius RE (2005) Cellular interactions in lymph node development. J Immunol 174(1):21–25 Dejardin E, Droin NM, Delhase M, Haas E, Cao Y, Makris C, Li ZW, Karin M, Ware CF, Green DR (2002) The lymphotoxin-beta receptor induces different patterns of gene expression via two NF-kappaB pathways. Immunity 17(4):525–535 Ngo VN, Korner H, Gunn MD, Schmidt KN, Riminton DS, Cooper MD, Browning JL, Sedgwick JD, Cyster JG (1999) Lymphotoxin alpha/beta and tumor necrosis factor are required for stromal cell expression of homing chemokines in B and T cell areas of the spleen. J Exp Med 189(2):403–412 Kim MY, McConnell FM, Gaspal FM, White A, Glanville SH, Bekiaris V, Walker LS, Caamano J, Jenkinson E, Anderson G, Lane PJ (2007) Function of CD4+ CD3− cells in relation to B- and T-zone stroma in spleen. Blood 109(4):1602–1610 Ohl L, Henning G, Krautwald S, Lipp M, Hardtke S, Bernhardt G, Pabst O, Forster R (2003) Cooperating mechanisms of CXCR5 and CCR7 in development and organization of secondary lymphoid organs. J Exp Med 197(9):1199–1204 Winter S, Loddenkemper C, Aebischer A, Rabel K, Hoffmann K, Meyer TF, Lipp M, Hopken UE (2010) The chemokine receptor CXCR5 is pivotal for ectopic mucosa-associated lymphoid tissue neogenesis in chronic Helicobacter pylori-induced inflammation. J Mol Med 88(11):1169–1180 Baeriswyl V, Christofori G (2009) The angiogenic switch in carcinogenesis. Semin Cancer Biol 19(5):329–337 Mantovani A, Savino B, Locati M, Zammataro L, Allavena P, Bonecchi R (2010) The chemokine system in cancer biology and therapy. Cytokine Growth Factor Rev 21(1):27–39 Mantovani A (2009) Cancer: inflaming metastasis. Nature 457(7225):36–37 Luboshits G, Shina S, Kaplan O, Engelberg S, Nass D, Lifshitz-Mercer B, Chaitchik S, Keydar I, Ben-Baruch A (1999) Elevated expression of the CC chemokine regulated on activation, normal T cell expressed and secreted (RANTES) in advanced breast carcinoma. Cancer Res 59(18):4681–4687 Ohta M, Kitadai Y, Tanaka S, Yoshihara M, Yasui W, Mukaida N, Haruma K, Chayama K (2002) Monocyte chemoattractant protein-1 expression correlates with macrophage infiltration and tumor vascularity in human esophageal squamous cell carcinomas. Int J Cancer 102(3):220–224 Popivanova BK, Kostadinova FI, Furuichi K, Shamekh MM, Kondo T, Wada T, Egashira K, Mukaida N (2009) Blockade of a chemokine, CCL2, reduces chronic colitis-associated carcinogenesis in mice. Cancer Res 69(19):7884–7892 Nibbs RJ, Gilchrist DS, King V, Ferra A, Forrow S, Hunter KD, Graham GJ (2007) The atypical chemokine receptor D6 suppresses the development of chemically induced skin tumors. J Clin Invest 117(7):1884–1892 Vetrano S, Borroni EM, Sarukhan A, Savino B, Bonecchi R, Correale C, Arena V, Fantini M, Roncalli M, Malesci A, Mantovani A, Locati M, Danese S (2010) The lymphatic system controls intestinal inflammation and inflammation-associated colon cancer through the chemokine decoy receptor D6. Gut 59(2):197–206 Collins CB, McNamee EN, Wermers JD, Lebsack MD, Rivera-Nieves J (2010) Chemokine decoy receptor D6 in inflammatory bowel disease (IBD) and IBD-associated colon cancer. Gut 59(2):151–152 Joyce JA, Pollard JW (2009) Microenvironmental regulation of metastasis. Nat Rev Cancer 9(4):239–252 Mantovani A, Sica A (2010) Macrophages, innate immunity and cancer: balance, tolerance, and diversity. Curr Opin Immunol 22(2):231–237 Bingle L, Brown NJ, Lewis CE (2002) The role of tumour-associated macrophages in tumour progression: implications for new anticancer therapies. J Pathol 196(3):254–265 Mantovani A, Sica A, Sozzani S, Allavena P, Vecchi A, Locati M (2004) The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol 25(12):677–686 Qian BZ, Pollard JW (2010) Macrophage diversity enhances tumor progression and metastasis. Cell 141(1):39–51 Hagemann T, Wilson J, Burke F, Kulbe H, Li NF, Pluddemann A, Charles K, Gordon S, Balkwill FR (2006) Ovarian cancer cells polarize macrophages toward a tumor-associated phenotype. J Immunol 176(8):5023–5032 Kim S, Takahashi H, Lin WW, Descargues P, Grivennikov S, Kim Y, Luo JL, Karin M (2009) Carcinoma-produced factors activate myeloid cells through TLR2 to stimulate metastasis. Nature 457(7225):102–106 Roca H, Varsos ZS, Sud S, Craig MJ, Ying C, Pienta KJ (2009) CCL2 and interleukin-6 promote survival of human CD11b+ peripheral blood mononuclear cells and induce M2-type macrophage polarization. J Biol Chem 284(49):34342–34354 Biswas SK, Gangi L, Paul S, Schioppa T, Saccani A, Sironi M, Bottazzi B, Doni A, Vincenzo B, Pasqualini F, Vago L, Nebuloni M, Mantovani A, Sica A (2006) A distinct and unique transcriptional program expressed by tumor-associated macrophages (defective NF-kappaB and enhanced IRF-3/STAT1 activation). Blood 107(5):2112–2122 Venneri MA, De Palma M, Ponzoni M, Pucci F, Scielzo C, Zonari E, Mazzieri R, Doglioni C, Naldini L (2007) Identification of proangiogenic TIE2-expressing monocytes (TEMs) in human peripheral blood and cancer. Blood 109(12):5276–5285 Sica A, Larghi P, Mancino A, Rubino L, Porta C, Totaro MG, Rimoldi M, Biswas SK, Allavena P, Mantovani A (2008) Macrophage polarization in tumour progression. Semin Cancer Biol 18(5):349–355 Ruhrberg C, De Palma M (2010) A double agent in cancer: deciphering macrophage roles in human tumors. Nat Med 16(8):861–862 Monti P, Leone BE, Marchesi F, Balzano G, Zerbi A, Scaltrini F, Pasquali C, Calori G, Pessi F, Sperti C, Di Carlo V, Allavena P, Piemonti L (2003) The CC chemokine MCP-1/CCL2 in pancreatic cancer progression: regulation of expression and potential mechanisms of antimalignant activity. Cancer Res 63(21):7451–7461 Allavena P, Garlanda C, Borrello MG, Sica A, Mantovani A (2008) Pathways connecting inflammation and cancer. Curr Opin Genet Dev 18(1):3–10 Sica A, Bronte V (2007) Altered macrophage differentiation and immune dysfunction in tumor development. J Clin Invest 117(5):1155–1166 Saccani A, Schioppa T, Porta C, Biswas SK, Nebuloni M, Vago L, Bottazzi B, Colombo MP, Mantovani A, Sica A (2006) p50 nuclear factor-kappaB overexpression in tumor-associated macrophages inhibits M1 inflammatory responses and antitumor resistance. Cancer Res 66(23):11432–11440 Porta C, Rimoldi M, Raes G, Brys L, Ghezzi P, Di Liberto D, Dieli F, Ghisletti S, Natoli G, De Baetselier P, Mantovani A, Sica A (2009) Tolerance and M2 (alternative) macrophage polarization are related processes orchestrated by p50 nuclear factor kappaB. Proc Natl Acad Sci U S A 106(35):14978–14983 Hagemann T, Lawrence T, McNeish I, Charles KA, Kulbe H, Thompson RG, Robinson SC, Balkwill FR (2008) “Re-educating” tumor-associated macrophages by targeting NF-kappaB. J Exp Med 205(6):1261–1268 Song L, Asgharzadeh S, Salo J, Engell K, Wu HW, Sposto R, Ara T, Silverman AM, DeClerck YA, Seeger RC, Metelitsa LS (2009) Valpha24-invariant NKT cells mediate antitumor activity via killing of tumor-associated macrophages. J Clin Invest 119(6):1524–1536 Luo Y, Zhou H, Krueger J, Kaplan C, Lee SH, Dolman C, Markowitz D, Wu W, Liu C, Reisfeld RA, Xiang R (2006) Targeting tumor-associated macrophages as a novel strategy against breast cancer. J Clin Invest 116(8):2132–2141 Mandruzzato S, Solito S, Falisi E, Francescato S, Chiarion-Sileni V, Mocellin S, Zanon A, Rossi CR, Nitti D, Bronte V, Zanovello P (2009) IL4Ralpha+ myeloid-derived suppressor cell expansion in cancer patients. J Immunol 182(10):6562–6568 Rodriguez PC, Ernstoff MS, Hernandez C, Atkins M, Zabaleta J, Sierra R, Ochoa AC (2009) Arginase I-producing myeloid-derived suppressor cells in renal cell carcinoma are a subpopulation of activated granulocytes. Cancer Res 69(4):1553–1560 Fridlender ZG, Sun J, Kim S, Kapoor V, Cheng G, Ling L, Worthen GS, Albelda SM (2009) Polarization of tumor-associated neutrophil phenotype by TGF-beta: “N1” versus “N2” TAN. Cancer Cell 16(3):183–194 Scapini P, Lapinet-Vera JA, Gasperini S, Calzetti F, Bazzoni F, Cassatella MA (2000) The neutrophil as a cellular source of chemokines. Immunol Rev 177:195–203 Gabrilovich DI, Nagaraj S (2009) Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol 9(3):162–174 Kryczek I, Banerjee M, Cheng P, Vatan L, Szeliga W, Wei S, Huang E, Finlayson E, Simeone D, Welling TH, Chang A, Coukos G, Liu R, Zou W (2009) Phenotype, distribution, generation, and functional and clinical relevance of Th17 cells in the human tumor environments. Blood 114(6):1141–1149 Ghiringhelli F, Apetoh L, Tesniere A, Aymeric L, Ma Y, Ortiz C, Vermaelen K, Panaretakis T, Mignot G, Ullrich E, Perfettini JL, Schlemmer F, Tasdemir E, Uhl M, Genin P, Civas A, Ryffel B, Kanellopoulos J, Tschopp J, Andre F, Lidereau R, McLaughlin NM, Haynes NM, Smyth MJ, Kroemer G, Zitvogel L (2009) Activation of the NLRP3 inflammasome in dendritic cells induces IL-1beta-dependent adaptive immunity against tumors. Nat Med 15(10):1170–1178 Merogi AJ, Marrogi AJ, Ramesh R, Robinson WR, Fermin CD, Freeman SM (1997) Tumor-host interaction: analysis of cytokines, growth factors, and tumor-infiltrating lymphocytes in ovarian carcinomas. Hum Pathol 28(3):321–331 Yoneda J, Kuniyasu H, Crispens MA, Price JE, Bucana CD, Fidler IJ (1998) Expression of angiogenesis-related genes and progression of human ovarian carcinomas in nude mice. J Natl Cancer Inst 90(6):447–454 Yatsunami J, Tsuruta N, Ogata K, Wakamatsu K, Takayama K, Kawasaki M, Nakanishi Y, Hara N, Hayashi S (1997) Interleukin-8 participates in angiogenesis in non-small cell, but not small cell carcinoma of the lung. Cancer Lett 120(1):101–108 Arenberg DA, Kunkel SL, Polverini PJ, Glass M, Burdick MD, Strieter RM (1996) Inhibition of interleukin-8 reduces tumorigenesis of human non-small cell lung cancer in SCID mice. J Clin Invest 97(12):2792–2802 Smith DR, Polverini PJ, Kunkel SL, Orringer MB, Whyte RI, Burdick MD, Wilke CA, Strieter RM (1994) Inhibition of interleukin 8 attenuates angiogenesis in bronchogenic carcinoma. J Exp Med 179(5):1409–1415 White ES, Flaherty KR, Carskadon S, Brant A, Iannettoni MD, Yee J, Orringer MB, Arenberg DA (2003) Macrophage migration inhibitory factor and CXC chemokine expression in non-small cell lung cancer: role in angiogenesis and prognosis. Clin Cancer Res 9(2):853–860 Bostwick DG, Iczkowski KA (1998) Microvessel density in prostate cancer: prognostic and therapeutic utility. Semin Urol Oncol 16(3):118–123 Moore BB, Arenberg DA, Stoy K, Morgan T, Addison CL, Morris SB, Glass M, Wilke C, Xue YY, Sitterding S, Kunkel SL, Burdick MD, Strieter RM (1999) Distinct CXC chemokines mediate tumorigenicity of prostate cancer cells. Am J Pathol 154(5):1503–1512 Shen H, Schuster R, Stringer KF, Waltz SE, Lentsch AB (2006) The Duffy antigen/receptor for chemokines (DARC) regulates prostate tumor growth. FASEB J 20(1):59–64 Mestas J, Burdick MD, Reckamp K, Pantuck A, Figlin RA, Strieter RM (2005) The role of CXCR2/CXCR2 ligand biological axis in renal cell carcinoma. J Immunol 175(8):5351–5357 Keeley EC, Mehrad B, Strieter RM (2011) Chemokines as mediators of tumor angiogenesis and neovascularization. Exp Cell Res 317(5):685–690 Galvez BG, Genis L, Matias-Roman S, Oblander SA, Tryggvason K, Apte SS, Arroyo AG (2005) Membrane type 1-matrix metalloproteinase is regulated by chemokines monocyte-chemoattractant protein-1/ccl2 and interleukin-8/CXCL8 in endothelial cells during angiogenesis. J Biol Chem 280(2):1292–1298 Stamatovic SM, Keep RF, Mostarica-Stojkovic M, Andjelkovic AV (2006) CCL2 regulates angiogenesis via activation of Ets-1 transcription factor. J Immunol 177(4):2651–2661 Strasly M, Doronzo G, Cappello P, Valdembri D, Arese M, Mitola S, Moore P, Alessandri G, Giovarelli M, Bussolino F (2004) CCL16 activates an angiogenic prog215.ram in vascular endothelial cells. Blood 103(1):40–49 Saji H, Koike M, Yamori T, Saji S, Seiki M, Matsushima K, Toi M (2001) Significant correlation of monocyte chemoattractant protein-1 expression with neovascularization and progression of breast carcinoma. Cancer 92(5):1085–1091 Ueno T, Toi M, Saji H, Muta M, Bando H, Kuroi K, Koike M, Inadera H, Matsushima K (2000) Significance of macrophage chemoattractant protein-1 in macrophage recruitment, angiogenesis, and survival in human breast cancer. Clin Cancer Res 6(8):3282–3289 Barcelos LS, Talvani A, Teixeira AS, Cassali GD, Andrade SP, Teixeira MM (2004) Production and in vivo effects of chemokines CXCL1–3/KC and CCL2/JE in a model of inflammatory angiogenesis in mice. Inflamm Res 53(10):576–584 Goede V, Brogelli L, Ziche M, Augustin HG (1999) Induction of inflammatory angiogenesis by monocyte chemoattractant protein-1. Int J Cancer 82(5):765–770 Salcedo R, Ponce ML, Young HA, Wasserman K, Ward JM, Kleinman HK, Oppenheim JJ, Murphy WJ (2000) Human endothelial cells express CCR2 and respond to MCP-1: direct role of MCP-1 in angiogenesis and tumor progression. Blood 96(1):34–40 Chavey C, Bibeau F, Gourgou-Bourgade S, Burlinchon S, Boissiere F, Laune D, Roques S, Lazennec G (2007) Oestrogen receptor negative breast cancers exhibit high cytokine content. Breast Cancer Res 9(1):R15 Singh S, Singh AP, Sharma B, Owen LB, Singh RK (2010) CXCL8 and its cognate receptors in melanoma progression and metastasis. Future Oncol 6(1):111–116 Richards BL, Eisma RJ, Spiro JD, Lindquist RL, Kreutzer DL (1997) Coexpression of interleukin-8 receptors in head and neck squamous cell carcinoma. Am J Surg 174(5):507–512 Singh RK, Gutman M, Radinsky R, Bucana CD, Fidler IJ (1994) Expression of interleukin 8 correlates with the metastatic potential of human melanoma cells in nude mice. Cancer Res 54(12):3242–3247 Ugurel S, Rappl G, Tilgen W, Reinhold U (2001) Increased serum concentration of angiogenic factors in malignant melanoma patients correlates with tumor progression and survival. J Clin Oncol 19(2):577–583 Arya M, Patel HR, Williamson M (2003) Chemokines: key players in cancer. Curr Med Res Opin 19(6):557–564 Yang TY, Chen SC, Leach MW, Manfra D, Homey B, Wiekowski M, Sullivan L, Jenh CH, Narula SK, Chensue SW, Lira SA (2000) Transgenic expression of the chemokine receptor encoded by human herpesvirus 8 induces an angioproliferative disease resembling Kaposi’s sarcoma. J Exp Med 191(3):445–454 Kawada K, Sonoshita M, Sakashita H, Takabayashi A, Yamaoka Y, Manabe T, Inaba K, Minato N, Oshima M, Taketo MM (2004) Pivotal role of CXCR3 in melanoma cell metastasis to lymph nodes. Cancer Res 64(11):4010–4017 Feng Y, Broder CC, Kennedy PE, Berger EA (1996) HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor. Science 272(5263):872–877 Ueda Y, Neel NF, Schutyser E, Raman D, Richmond A (2006) Deletion of the COOH-terminal domain of CXC chemokine receptor 4 leads to the down-regulation of cell-to-cell contact, enhanced motility and proliferation in breast carcinoma cells. Cancer Res 66(11):5665–5675 Zhou Y, Larsen PH, Hao C, Yong VW (2002) CXCR4 is a major chemokine receptor on glioma cells and mediates their survival. J Biol Chem 277(51):49481–49487 Ben-Baruch A (2008) Organ selectivity in metastasis: regulation by chemokines and their receptors. Clin Exp Metastasis 25(4):345–356 Bachelder RE, Wendt MA, Mercurio AM (2002) Vascular endothelial growth factor promotes breast carcinoma invasion in an autocrine manner by regulating the chemokine receptor CXCR4. Cancer Res 62(24):7203–7206 Helbig G, Christopherson KW, Bhat-Nakshatri P, Kumar S, Kishimoto H, Miller KD, Broxmeyer HE, Nakshatri H (2003) NF-kappaB promotes breast cancer cell migration and metastasis by inducing the expression of the chemokine receptor CXCR4. J Biol Chem 278(24):21631–21638 Salvucci O, Bouchard A, Baccarelli A, Deschenes J, Sauter G, Simon R, Bianchi R, Basik M (2006) The role of CXCR4 receptor expression in breast cancer: a large tissue microarray study. Breast Cancer Res Treat 97(3):275–283 Muller A, Homey B, Soto H, Ge N, Catron D, Buchanan ME, McClanahan T, Murphy E, Yuan W, Wagner SN, Barrera JL, Mohar A, Verastegui E, Zlotnik A (2001) Involvement of chemokine receptors in breast cancer metastasis. Nature 410(6824):50–56 Lapidot T (2001) Mechanism of human stem cell migration and repopulation of NOD/SCID and B2mnull NOD/SCID mice. The role of SDF-1/CXCR4 interactions. Ann N Y Acad Sci 938:83–95 Nagasawa T (2000) A chemokine, SDF-1/PBSF, and its receptor, CXC chemokine receptor 4, as mediators of hematopoiesis. Int J Hematol 72(4):408–411 Furusato B, Mohamed A, Uhlen M, Rhim JS (2010) CXCR4 and cancer. Pathol Int 60(7):497–505 Balkwill F (2004) The significance of cancer cell expression of the chemokine receptor CXCR4. Semin Cancer Biol 14(3):171–179 Bertolini F, Dell’Agnola C, Mancuso P, Rabascio C, Burlini A, Monestiroli S, Gobbi A, Pruneri G, Martinelli G (2002) CXCR4 neutralization, a novel therapeutic approach for non-Hodgkin’s lymphoma. Cancer Res 62(11):3106–3112 Rubin JB, Kung AL, Klein RS, Chan JA, Sun Y, Schmidt K, Kieran MW, Luster AD, Segal RA (2003) A small-molecule antagonist of CXCR4 inhibits intracranial growth of primary brain tumors. Proc Natl Acad Sci U S A 100(23):13513–13518 Wiley HE, Gonzalez EB, Maki W, Wu MT, Hwang ST (2001) Expression of CC chemokine receptor-7 and regional lymph node metastasis of B16 murine melanoma. J Natl Cancer Inst 93(21):1638–1643 Cabioglu N, Yazici MS, Arun B, Broglio KR, Hortobagyi GN, Price JE, Sahin A (2005) CCR7 and CXCR4 as novel biomarkers predicting axillary lymph node metastasis in T1 breast cancer. Clin Cancer Res 11(16):5686–5693 Wilson JL, Burchell J, Grimshaw MJ (2006) Endothelins induce CCR7 expression by breast tumor cells via endothelin receptor A and hypoxia-inducible factor-1. Cancer Res 66(24):11802–11807 Cavanagh LL, Von Andrian UH (2002) Travellers in many guises: the origins and destinations of dendritic cells. Immunol Cell Biol 80(5):448–462 Mashino K, Sadanaga N, Yamaguchi H, Tanaka F, Ohta M, Shibuta K, Inoue H, Mori M (2002) Expression of chemokine receptor CCR7 is associated with lymph node metastasis of gastric carcinoma. Cancer Res 62(10):2937–2941 Ding Y, Shimada Y, Maeda M, Kawabe A, Kaganoi J, Komoto I, Hashimoto Y, Miyake M, Hashida H, Imamura M (2003) Association of CC chemokine receptor 7 with lymph node metastasis of esophageal squamous cell carcinoma. Clin Cancer Res 9(9):3406–3412 Ishida T, Utsunomiya A, Iida S, Inagaki H, Takatsuka Y, Kusumoto S, Takeuchi G, Shimizu S, Ito M, Komatsu H, Wakita A, Eimoto T, Matsushima K, Ueda R (2003) Clinical significance of CCR4 expression in adult T-cell leukemia/lymphoma: its close association with skin involvement and unfavorable outcome. Clin Cancer Res 9(10 Pt 1):3625–3634 Homey B, Wang W, Soto H, Buchanan ME, Wiesenborn A, Catron D, Muller A, McClanahan TK, Dieu-Nosjean MC, Orozco R, Ruzicka T, Lehmann P, Oldham E, Zlotnik A (2000) Cutting edge: the orphan chemokine receptor G protein-coupled receptor-2 (GPR-2, CCR10) binds the skin-associated chemokine CCL27 (CTACK/ALP/ILC). J Immunol 164(7):3465–3470 Simonetti O, Goteri G, Lucarini G, Filosa A, Pieramici T, Rubini C, Biagini G, Offidani A (2006) Potential role of CCL27 and CCR10 expression in melanoma progression and immune escape. Eur J Cancer 42(8):1181–1187 Murakami T, Cardones AR, Finkelstein SE, Restifo NP, Klaunberg BA, Nestle FO, Castillo SS, Dennis PA, Hwang ST (2003) Immune evasion by murine melanoma mediated through CC chemokine receptor-10. J Exp Med 198(9):1337–1347 Harasawa H, Yamada Y, Hieshima K, Jin Z, Nakayama T, Yoshie O, Shimizu K, Hasegawa H, Hayashi T, Imaizumi Y, Ikeda S, Soda H, Atogami S, Takasaki Y, Tsukasaki K, Tomonaga M, Murata K, Sugahara K, Tsuruda K, Kamihira S (2006) Survey of chemokine receptor expression reveals frequent co-expression of skin-homing CCR4 and CCR10 in adult T-cell leukemia/lymphoma. Leuk Lymphoma 47(10):2163–2173 Kleinhans M, Tun-Kyi A, Gilliet M, Kadin ME, Dummer R, Burg G, Nestle FO (2003) Functional expression of the eotaxin receptor CCR3 in CD30+ cutaneous T-cell lymphoma. Blood 101(4):1487–1493 Martins-Green M, Tilley C, Schwarz R, Hatier C, Bissell MJ (1991) Wound-factor-induced and cell cycle phase-dependent expression of 9E3/CEF4, the avian gro gene. Cell Regul 2(9):739–752 Cao Y, Chen C, Weatherbee JA, Tsang M, Folkman J (1995) gro-beta, a -C-X-C- chemokine, is an angiogenesis inhibitor that suppresses the growth of Lewis lung carcinoma in mice. J Exp Med 182(6):2069–2077 Luan J, Shattuck-Brandt R, Haghnegahdar H, Owen JD, Strieter R, Burdick M, Nirodi C, Beauchamp D, Johnson KN, Richmond A (1997) Mechanism and biological significance of constitutive expression of MGSA/GRO chemokines in malignant melanoma tumor progression. J Leukoc Biol 62(5):588–597 Arenberg DA, Keane MP, DiGiovine B, Kunkel SL, Morris SB, Xue YY, Burdick MD, Glass MC, Iannettoni MD, Strieter RM (1998) Epithelial-neutrophil activating peptide (ENA-78) is an important angiogenic factor in non-small cell lung cancer. J Clin Invest 102(3):465–472 Van Coillie E, Van Aelst I, Wuyts A, Vercauteren R, Devos R, De Wolf-Peeters C, Van Damme J, Opdenakker G (2001) Tumor angiogenesis induced by granulocyte chemotactic protein-2 as a countercurrent principle. Am J Pathol 159(4):1405–1414 Ahuja SK, Murphy PM (1996) The CXC chemokines growth-regulated oncogene (GRO) alpha, GRObeta, GROgamma, neutrophil-activating peptide-2, and epithelial cell-derived neutrophil-activating peptide-78 are potent agonists for the type B, but not the type A, human interleukin-8 receptor. J Biol Chem 271(34):20545–20550 Koch AE, Polverini PJ, Kunkel SL, Harlow LA, DiPietro LA, Elner VM, Elner SG, Strieter RM (1992) Interleukin-8 as a macrophage-derived mediator of angiogenesis. Science 258(5089):1798–1801 Salcedo R, Young HA, Ponce ML, Ward JM, Kleinman HK, Murphy WJ, Oppenheim JJ (2001) Eotaxin (CCL11) induces in vivo angiogenic responses by human CCR3+ endothelial cells. J Immunol 166(12):7571–7578 Luster AD, Greenberg SM, Leder P (1995) The IP-10 chemokine binds to a specific cell surface heparan sulfate site shared with platelet factor 4 and inhibits endothelial cell proliferation. J Exp Med 182(1):219–231 Shellenberger TD, Wang M, Gujrati M, Jayakumar A, Strieter RM, Burdick MD, Ioannides CG, Efferson CL, El-Naggar AK, Roberts D, Clayman GL, Frederick MJ (2004) BRAK/CXCL14 is a potent inhibitor of angiogenesis and a chemotactic factor for immature dendritic cells. Cancer Res 64(22):8262–8270