Role of the tumor microenvironment in tumor progression and the clinical applications (Review)

Oncology Reports - Tập 35 Số 5 - Trang 2499-2515 - 2016
Yao Yuan1, Yuchen Jiang1, Chongkui Sun1, Qianming Chen1
1State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, P.R. China

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Hanahan, 2000, The hallmarks of cancer, Cell, 100, 57, 10.1016/S0092-8674(00)81683-9

Hanahan, 2011, Hallmarks of cancer: The next generation, Cell, 144, 646, 10.1016/j.cell.2011.02.013

Hanahan, 2012, Accessories to the crime: Functions of cells recruited to the tumor microenvironment, Cancer Cell, 21, 309, 10.1016/j.ccr.2012.02.022

Cirri, 2011, Cancer associated fibroblasts: The dark side of the coin, Am J Cancer Res, 1, 482

Gabrilovich, 2012, Coordinated regulation of myeloid cells by Tumours, Nat Rev Immunol, 12, 253, 10.1038/nri3175

Cheng, 2013, Glioblastoma stem cells generate vascular pericytes to support vessel function and tumor growth, Cell, 153, 139, 10.1016/j.cell.2013.02.021

Cornil, 1991, Fibroblast cell interactions with human melanoma cells affect tumor cell growth as a function of tumor progression, Proc Natl Acad Sci USA, 88, 6028, 10.1073/pnas.88.14.6028

Räsänen, 2010, Activation of fibroblasts in cancer stroma, Exp Cell Res, 316, 2713, 10.1016/j.yexcr.2010.04.032

Lu, 1992, Interleukin 6: A fibroblast-derived growth inhibitor of human melanoma cells from early but not advanced stages of tumor progression, Proc Natl Acad Sci USA, 89, 9215, 10.1073/pnas.89.19.9215

Leonardi, 2012, The tumor microenvironment in hepatocellular carcinoma (review), Int J Oncol, 40, 1733

Rønnov-Jessen, 1993, Induction of alpha-smooth muscle actin by transforming growth factor-beta 1 in quiescent human breast gland fibroblasts. Implications for myofibroblast generation in breast neoplasia, Lab Invest, 68, 696

Postlethwaite, 1987, Stimulation of the chemotactic migration of human fibroblasts by transforming growth factor beta, J Exp Med, 165, 251, 10.1084/jem.165.1.251

Mayo, 2002, PTEN protects p53 from Mdm2 and sensitizes cancer cells to chemotherapy, J Biol Chem, 277, 5484, 10.1074/jbc.M108302200

Erez, 2010, Cancer-associated fibroblasts are activated in incipient neoplasia to orchestrate tumor-promoting inflammation in an NF-kappaB-dependent manner, Cancer Cell, 17, 135, 10.1016/j.ccr.2009.12.041

De Wever, 2008, Stromal myofibroblasts are drivers of invasive cancer growth, Int J Cancer, 123, 2229, 10.1002/ijc.23925

Schmitt-Gräff, 1994, Heterogeneity of myofibroblast phenotypic features: An example of fibroblastic cell plasticity, Virchows Arch, 425, 3, 10.1007/BF00193944

Tlsty, 2001, Know thy neighbor: Stromal cells can contribute oncogenic signals, Curr Opin Genet Dev, 11, 54, 10.1016/S0959-437X(00)00156-8

Skalli, 1989, Alpha-smooth muscle actin, a differentiation marker of smooth muscle cells, is present in microfilamentous bundles of pericytes, J Histochem Cytochem, 37, 315, 10.1177/37.3.2918221

De Wever, 2003, Role of tissue stroma in cancer cell invasion, J Pathol, 200, 429, 10.1002/path.1398

Pittenger, 1999, Multilineage potential of adult human mesenchymal stem cells, Science, 284, 143, 10.1126/science.284.5411.143

Rattigan, 2010, Interleukin 6 mediated recruitment of mesenchymal stem cells to the hypoxic tumor milieu, Exp Cell Res, 316, 3417, 10.1016/j.yexcr.2010.07.002

Karnoub, 2007, Mesenchymal stem cells within tumour stroma promote breast cancer metastasis, Nature, 449, 557, 10.1038/nature06188

Zeisberg, 2007, Endothelial-to-mesenchymal transition contributes to cardiac fibrosis, Nat Med, 13, 952, 10.1038/nm1613

Zeisberg, 2007, Discovery of endothelial to mesenchymal transition as a source for carcinoma-associated fibroblasts, Cancer Res, 67, 10123, 10.1158/0008-5472.CAN-07-3127

Petersen, 2001, The plasticity of human breast carcinoma cells is more than epithelial to mesenchymal conversion, Breast Cancer Res, 3, 213, 10.1186/bcr298

Petersen, 2003, Epithelial to mesenchymal transition in human breast cancer can provide a nonmalignant stroma, Am J Pathol, 162, 391, 10.1016/S0002-9440(10)63834-5

Kurose, 2002, Frequent somatic mutations in PTEN and TP53 are mutually exclusive in the stroma of breast carcinomas, Nat Genet, 32, 355, 10.1038/ng1013

Orimo, 2006, Stromal fibroblasts in cancer: A novel tumor-promoting cell type, Cell Cycle, 5, 1597, 10.4161/cc.5.15.3112

Bronisz, 2011, Reprogramming of the tumour microenvironment by stromal PTEN-regulated miR-320, Nat Cell Biol, 14, 159, 10.1038/ncb2396

Sun, 2014, IL-6 secreted by cancer-associated fibroblasts induces tamoxifen resistance in luminal breast cancer, Oncogene, 10.1038/onc.2014.158

Sica, 2010, Role of tumour-associated macrophages in cancer-related inflammation, Exp Oncol, 32, 153

Sica, 2008, Macrophage polarization in tumour progression, Semin Cancer Biol, 18, 349, 10.1016/j.semcancer.2008.03.004

Lin, 2001, Colony-stimulating factor 1 promotes progression of mammary tumors to malignancy, J Exp Med, 193, 727, 10.1084/jem.193.6.727

Nesbit, 2001, Low-level monocyte chemoattractant protein-1 stimulation of monocytes leads to tumor formation in nontumorigenic melanoma cells, J Immunol, 166, 6483, 10.4049/jimmunol.166.11.6483

Schmid, 2011, Receptor tyrosine kinases and TLR/IL1Rs unexpectedly activate myeloid cell PI3kγ, a single convergent point promoting tumor inflammation and progression, Cancer Cell, 19, 715, 10.1016/j.ccr.2011.04.016

Balkwill, 2004, Cancer and the chemokine network, Nat Rev Cancer, 4, 540, 10.1038/nrc1388

Qian, 2011, CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis, Nature, 475, 222, 10.1038/nature10138

Mizutani, 2009, The chemokine CCL2 increases prostate tumor growth and bone metastasis through macrophage and osteoclast recruitment, Neoplasia, 11, 1235, 10.1593/neo.09988

Acharyya, 2012, A CXCL1 paracrine network links cancer chemoresistance and metastasis, Cell, 150, 165, 10.1016/j.cell.2012.04.042

Shields, 2010, Induction of lymphoidlike stroma and immune escape by tumors that express the chemokine CCL21, Science, 328, 749, 10.1126/science.1185837

Cremer, 2012, Tumor microenvironment in NSCLC suppresses NK cells function, Oncoimmunology, 1, 244, 10.4161/onci.1.2.18309

Zhao, 2012, TNF signaling drives myeloid-derived suppressor cell accumulation, J Clin Invest, 122, 4094, 10.1172/JCI64115

Bayne, 2012, Tumor-derived granulocyte-macrophage colony-stimulating factor regulates myeloid inflammation and T cell immunity in pancreatic cancer, Cancer Cell, 21, 822, 10.1016/j.ccr.2012.04.025

Würth, 2014, CXCL12 modulation of CXCR4 and CXCR7 activity in human glioblastoma stem-like cells and regulation of the tumor micro-environment, Front Cell Neurosci, 8, 144

Bergers, 2003, Tumorigenesis and the angiogenic switch, Nat Rev Cancer, 3, 401, 10.1038/nrc1093

Bertolini, 2006, The multifaceted circulating endothelial cell in cancer: Towards marker and target identification, Nat Rev Cancer, 6, 835, 10.1038/nrc1971

Volm, 1997, Prognostic value of vascular endothelial growth factor and its receptor FLT-1 in squamous cell lung cancer, Int J Cancer, 74, 64, 10.1002/(SICI)1097-0215(19970220)74:1<64::AID-IJC11>3.0.CO;2-I

Yoshiji, 1996, Expression of vascular endothelial growth factor, its receptor, and other angiogenic factors in human breast cancer, Cancer Res, 56, 2013

Olson, 1994, Vascular permeability factor gene expression in normal and neoplastic human ovaries, Cancer Res, 54, 276

Brown, 1993, Increased expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in kidney and bladder carcinomas, Am J Pathol, 143, 1255

Asahara, 1999, VEGF contributes to postnatal neovascularization by mobilizing bone marrow-derived endothelial progenitor cells, EMBO J, 18, 3964, 10.1093/emboj/18.14.3964

Png, 2011, A microRNA regulon that mediates endothelial recruitment and metastasis by cancer cells, Nature, 481, 190, 10.1038/nature10661

Zeng, 2014, The cross talk between cGMP signal pathway and PKC in pulmonary endothelial cell angiogenesis, Int J Mol Sci, 15, 10185, 10.3390/ijms150610185

Karar, 2011, PI3K/AKT/mTOR pathway in angiogenesis, Front Mol Neurosci, 4, 51, 10.3389/fnmol.2011.00051

Wang, 2014, mTOR co-targeting in cetuximab resistance in head and neck cancers harboring PIK3CA and RAS mutations, J Natl Cancer Inst, 106, dju215, 10.1093/jnci/dju215

Patel, 2011, Decreased lymphangiogenesis and lymph node metastasis by mTOR inhibition in head and neck cancer, Cancer Res, 71, 7103, 10.1158/0008-5472.CAN-10-3192

Oft, 1998, TGFbeta signaling is necessary for carcinoma cell invasiveness and metastasis, Curr Biol, 8, 1243, 10.1016/S0960-9822(07)00533-7

Biswas, 2007, Inhibition of TGF-beta with neutralizing antibodies prevents radiation-induced acceleration of metastatic cancer progression, J Clin Invest, 117, 1305, 10.1172/JCI30740

Padua, 2008, TGFbeta primes breast tumors for lung metastasis seeding through angiopoietin-like 4, Cell, 133, 66, 10.1016/j.cell.2008.01.046

Siegel, 2003, Transforming growth factor beta signaling impairs Neu-induced mammary tumorigenesis while promoting pulmonary metastasis, Proc Natl Acad Sci USA, 100, 8430, 10.1073/pnas.0932636100

Yin, 1999, TGF-beta signaling blockade inhibits PTHrP secretion by breast cancer cells and bone metastases development, J Clin Invest, 103, 197, 10.1172/JCI3523

Kang, 2005, Breast cancer bone metastasis mediated by the Smad tumor suppressor pathway, Proc Natl Acad Sci USA, 102, 13909, 10.1073/pnas.0506517102

Labelle, 2011, Direct signaling between platelets and cancer cells induces an epithelial-mesenchymal-like transition and promotes metastasis, Cancer Cell, 20, 576, 10.1016/j.ccr.2011.09.009

Nakamura, 1989, Molecular cloning and expression of human hepatocyte growth factor, Nature, 342, 440, 10.1038/342440a0

Birchmeier, 2003, Met, metastasis, motility and more, Nat Rev Mol Cell Biol, 4, 915, 10.1038/nrm1261

Matsumoto, 2006, Hepatocyte growth factor and the met system as a mediator of tumor-stromal interactions, Int J Cancer, 119, 477, 10.1002/ijc.21808

Wilson, 2012, Widespread potential for growth-factor-driven resistance to anticancer kinase inhibitors, Nature, 487, 505, 10.1038/nature11249

Straussman, 2012, Tumour micro-environment elicits innate resistance to RAF inhibitors through HGF secretion, Nature, 487, 500, 10.1038/nature11183

Zhou, 2015, Generation of head and neck cancer patient-derived xenografts with in vivo acquired cetuximab resistance, Clin Cancer Res, 21, B39, 10.1158/1557-3265.PMS14-B39

Rossi, 2000, The biology of chemokines and their receptors, Annu Rev Immunol, 18, 217, 10.1146/annurev.immunol.18.1.217

Murphy, 2000, International union of pharmacology. XXII Nomenclature for chemokine receptors, Pharmacol Rev, 52, 145

Zlotnik, 2000, Chemokines: A new classification system and their role in immunity, Immunity, 12, 121, 10.1016/S1074-7613(00)80165-X

Dhawan, 2002, Role of CXCL1 in tumorigenesis of melanoma, J Leukoc Biol, 72, 9, 10.1189/jlb.72.1.9

Wang, 2006, CXCL1 induced by prostaglandin E2 promotes angiogenesis in colorectal cancer, J Exp Med, 203, 941, 10.1084/jem.20052124

Karunagaran, 1996, ErbB-2 is a common auxiliary subunit of NDF and EGF receptors: Implications for breast cancer, EMBO J, 15, 254, 10.1002/j.1460-2075.1996.tb00356.x

Conti, 2004, CCL2 (monocyte chemoattractant protein-1) and cancer, Semin Cancer Biol, 14, 149, 10.1016/j.semcancer.2003.10.009

Craig, 2006, CCL2 (monocyte chemoattractant protein-1) in cancer bone metastases, Cancer Metastasis Rev, 25, 611, 10.1007/s10555-006-9027-x

Popivanova, 2009, Blockade of a chemokine, CCL2, reduces chronic colitis-associated carcinogenesis in mice, Cancer Res, 69, 7884, 10.1158/0008-5472.CAN-09-1451

Rottiers, 2012, MicroRNAs in metabolism and metabolic disorders, Nat Rev Mol Cell Biol, 13, 239, 10.1038/nrm3313

Krützfeldt, 2006, MicroRNAs: A new class of regulatory genes affecting metabolism, Cell Metab, 4, 9, 10.1016/j.cmet.2006.05.009

Calin, 2006, MicroRNA signatures in human cancers, Nat Rev Cancer, 6, 857, 10.1038/nrc1997

Kosaka, 2010, Secretory mechanisms and intercellular transfer of microRNAs in living cells, J Biol Chem, 285, 17442, 10.1074/jbc.M110.107821

Zhang, 2012, Secretory miRNAs as novel cancer biomarkers, Biochim Biophys Acta, 1826, 32

Xu, 2013, The role of exosomes and microRNAs in senescence and aging, Adv Drug Deliv Rev, 65, 368, 10.1016/j.addr.2012.07.010

Kosaka, 2012, Competitive interactions of cancer cells and normal cells via secretory microRNAs, J Biol Chem, 287, 1397, 10.1074/jbc.M111.288662

Yang, 2011, Microvesicles secreted by macrophages shuttle invasion-potentiating microRNAs into breast cancer cells, Mol Cancer, 10, 117, 10.1186/1476-4598-10-117

Fabbri, 2012, MicroRNAs bind to Toll-like receptors to induce prometastatic inflammatory response, Proc Natl Acad Sci USA, 109, E2110, 10.1073/pnas.1209414109

Roth, 2010, Circulating microRNAs as blood-based markers for patients with primary and metastatic breast cancer, Breast Cancer Res, 12, R90, 10.1186/bcr2766

Mitchell, 2008, Circulating microRNAs as stable blood-based markers for cancer detection, Proc Natl Acad Sci USA, 105, 10513, 10.1073/pnas.0804549105

Cairns, 2011, Regulation of cancer cell metabolism, Nat Rev Cancer, 11, 85, 10.1038/nrc2981

Vander Heiden, 2009, Understanding the Warburg effect: The metabolic requirements of cell proliferation, Science, 324, 1029, 10.1126/science.1160809

Lunt, 2011, Aerobic glycolysis: Meeting the metabolic requirements of cell proliferation, Annu Rev Cell Dev Biol, 27, 441, 10.1146/annurev-cellbio-092910-154237

Riemann, 2011, Acidic environment leads to ROS-induced MAPK signaling in cancer cells, PLoS One, 6, e22445, 10.1371/journal.pone.0022445

Fischer, 2007, Inhibitory effect of tumor cell-derived lactic acid on human t cells, Blood, 109, 3812, 10.1182/blood-2006-07-035972

Walenta, 2004, Lactate: Mirror and motor of tumor malignancy, Semin Radiat Oncol, 14, 267, 10.1016/j.semradonc.2004.04.004

Rattigan, 2012, Lactate is a mediator of metabolic cooperation between stromal carcinoma associated fibroblasts and glycolytic tumor cells in the tumor microenvironment, Exp Cell Res, 318, 326, 10.1016/j.yexcr.2011.11.014

Végran, 2011, Lactate influx through the endothelial cell monocarboxylate transporter MCT1 supports an NF-κB/IL-8 pathway that drives tumor angiogenesis, Cancer Res, 71, 2550, 10.1158/0008-5472.CAN-10-2828

Semenza, 2008, Tumor metabolism: Cancer cells give and take lactate, J Clin Invest, 118, 3835

Feron, 2009, Pyruvate into lactate and back: From the Warburg effect to symbiotic energy fuel exchange in cancer cells, Radiother Oncol, 92, 329, 10.1016/j.radonc.2009.06.025

Sonveaux, 2008, Targeting lactate-fueled respiration selectively kills hypoxic tumor cells in mice, J Clin Invest, 118, 3930

Koukourakis, 2006, Comparison of metabolic pathways between cancer cells and stromal cells in colorectal carcinomas: A metabolic survival role for tumor-associated stroma, Cancer Res, 66, 632, 10.1158/0008-5472.CAN-05-3260

Nieman, 2011, Adipocytes promote ovarian cancer metastasis and provide energy for rapid tumor growth, Nat Med, 17, 1498, 10.1038/nm.2492

Marie, 2011, Metabolism and brain cancer, Clinics (Sao Paulo), 66, 33, 10.1590/S1807-59322011001300005

Hirayama, 2009, Quantitative metabolome profiling of colon and stomach cancer microenvironment by capillary electrophoresis time-of-flight mass spectrometry, Cancer Res, 69, 4918, 10.1158/0008-5472.CAN-08-4806

Ko, 2011, Glutamine fuels a vicious cycle of autophagy in the tumor stroma and oxidative mitochondrial metabolism in epithelial cancer cells: Implications for preventing chemotherapy resistance, Cancer Biol Ther, 12, 1085, 10.4161/cbt.12.12.18671

Filipp, 2012, Glutamine-fueled mitochondrial metabolism is decoupled from glycolysis in melanoma, Pigment Cell Melanoma Res, 25, 732, 10.1111/pcmr.12000

Jain, 2012, Metabolite profiling identifies a key role for glycine in rapid cancer cell proliferation, Science, 336, 1040, 10.1126/science.1218595

Okamoto, 1996, Overexpression of human mutT homologue gene messenger RNA in renal-cell carcinoma: evidence of persistent oxidative stress in cancer, Int J Cancer, 65, 437, 10.1002/(SICI)1097-0215(19960208)65:4<437::AID-IJC7>3.0.CO;2-Y

Gackowski, 2002, Persistent oxidative stress in colorectal carcinoma patients, Int J Cancer, 101, 395, 10.1002/ijc.10610

Toyokuni, 1995, Persistent oxidative stress in cancer, FEBS Lett, 358, 1, 10.1016/0014-5793(94)01368-B

Zhou, 2003, Free radical stress in chronic lymphocytic leukemia cells and its role in cellular sensitivity to ROS-generating anticancer agents, Blood, 101, 4098, 10.1182/blood-2002-08-2512

Szatrowski, 1991, Production of large amounts of hydrogen peroxide by human tumor cells, Cancer Res, 51, 794

Grivennikov, 2010, Immunity, inflammation, and cancer, Cell, 140, 883, 10.1016/j.cell.2010.01.025

Ishikawa, 2008, ROS-generating mitochondrial DNA mutations can regulate tumor cell metastasis, Science, 320, 661, 10.1126/science.1156906

Trachootham, 2009, Targeting cancer cells by ROS-mediated mechanisms: A radical therapeutic approach?, Nat Rev Drug Discov, 8, 579, 10.1038/nrd2803

Martinez-Outschoorn, 2011, Cancer cells metabolically 'fertilize' the tumor microenvironment with hydrogen peroxide, driving the Warburg effect: Implications for Pet imaging of human tumors, Cell Cycle, 10, 2504, 10.4161/cc.10.15.16585

Mathew, 2007, Role of autophagy in cancer, Nat Rev Cancer, 7, 961, 10.1038/nrc2254

Baehrecke, 2005, Autophagy: Dual roles in life and death?, Nat Rev Mol Cell Biol, 6, 505, 10.1038/nrm1666

Eisenberg-Lerner, 2009, The paradox of autophagy and its implication in cancer etiology and therapy, Apoptosis, 14, 376, 10.1007/s10495-008-0307-5

Pavlides, 2010, The autophagic tumor stroma model of cancer: Role of oxidative stress and ketone production in fueling tumor cell metabolism, Cell Cycle, 9, 3485, 10.4161/cc.9.17.12721

Martinez-Outschoorn, 2010, Oxidative stress in cancer associated fibroblasts drives tumor-stroma co-evolution: A new paradigm for understanding tumor metabolism, the field effect and genomic instability in cancer cells, Cell Cycle, 9, 3256, 10.4161/cc.9.16.12553

Bonuccelli, 2010, Ketones and lactate 'fuel' tumor growth and metastasis: Evidence that epithelial cancer cells use oxidative mitochondrial metabolism, Cell Cycle, 9, 3506, 10.4161/cc.9.17.12731

Martinez-Outschoorn, 2010, Autophagy in cancer associated fibroblasts promotes tumor cell survival: Role of hypoxia, HIF1 induction and NFκB activation in the tumor stromal microenvironment, Cell Cycle, 9, 3515, 10.4161/cc.9.17.12928

Chiavarina, 2010, HIF1-alpha functions as a tumor promoter in cancer associated fibroblasts, and as a tumor suppressor in breast cancer cells: Autophagy drives compartment-specific oncogenesis, Cell Cycle, 9, 3534, 10.4161/cc.9.17.12908

Martinez-Outschoorn, 2010, The autophagic tumor stroma model of cancer or 'battery-operated tumor growth': A simple solution to the autophagy paradox, Cell Cycle, 9, 4297, 10.4161/cc.9.21.13817

Salem, 2012, Two-compartment tumor metabolism: Autophagy in the tumor microenvironment and oxidative mitochondrial metabolism (OXPHOS) in cancer cells, Cell Cycle, 11, 2545, 10.4161/cc.20920

Zhang, 2012, Stromal control of cystine metabolism promotes cancer cell survival in chronic lymphocytic leukaemia, Nat Cell Biol, 14, 276, 10.1038/ncb2432

Carmeliet, 2011, Molecular mechanisms and clinical applications of angiogenesis, Nature, 473, 298, 10.1038/nature10144

Risau, 1997, Mechanisms of angiogenesis, Nature, 386, 671, 10.1038/386671a0

Carmeliet, 2000, Angiogenesis in cancer and other diseases, Nature, 407, 249, 10.1038/35025220

Leek, 1996, Association of macrophage infiltration with angiogenesis and prognosis in invasive breast carcinoma, Cancer Res, 56, 4625

Polverini, 1984, Induction of neovascularization in vivo and endothelial proliferation in vitro by tumor-associated macrophages, Lab Invest, 51, 635

O'Sullivan, 1993, Secretion of epidermal growth factor by macrophages associated with breast carcinoma, Lancet, 342, 148, 10.1016/0140-6736(93)91348-P

Lewis, 1995, Cytokine regulation of angiogenesis in breast cancer: The role of tumor-associated macrophages, J Leukoc Biol, 57, 747, 10.1002/jlb.57.5.747

Harmey, 1998, Regulation of macrophage production of vascular endothelial growth factor (VEGF) by hypoxia and transforming growth factor beta-1, Ann Surg Oncol, 5, 271, 10.1007/BF02303785

Stockmann, 2008, Deletion of vascular endothelial growth factor in myeloid cells accelerates tumori-genesis, Nature, 456, 814, 10.1038/nature07445

Bingle, 2006, Macrophages promote angiogenesis in human breast tumour spheroids in vivo, Br J Cancer, 94, 101, 10.1038/sj.bjc.6602901

Voronov, 2003, IL-1 is required for tumor invasiveness and angiogenesis, Proc Natl Acad Sci USA, 100, 2645, 10.1073/pnas.0437939100

Chen, 2011, Tumor-associated macrophages promote angiogenesis and melanoma growth via adrenomedullin in a paracrine and autocrine manner, Clin Cancer Res, 17, 7230, 10.1158/1078-0432.CCR-11-1354

Mazzieri, 2011, Targeting the ANG2/TIE2 axis inhibits tumor growth and metastasis by impairing angiogenesis and disabling rebounds of proangiogenic myeloid cells, Cancer Cell, 19, 512, 10.1016/j.ccr.2011.02.005

Hughes, 2011, Role of tumour-associated macrophages in the regulation of angiogenesis, Tumour-Associated Macrophages, 17, 10.1007/978-1-4614-0662-4_2

Giraudo, 2004, An amino-bisphosphonate targets MMP-9-expressing macrophages and angiogenesis to impair cervical carcinogenesis, J Clin Invest, 114, 623, 10.1172/JCI200422087

Li, 2012, Activated macrophages induce neovascularization through upregulation of MMP-9 and VEGF in rat corneas, Cornea, 31, 1028, 10.1097/ICO.0b013e31823f8b40

Houghton, 2006, Macrophage elastase (matrix metalloproteinase-12) suppresses growth of lung metastases, Cancer Res, 66, 6149, 10.1158/0008-5472.CAN-04-0297

Guo, 2008, Stromal fibroblasts activated by tumor cells promote angiogenesis in mouse gastric cancer, J Biol Chem, 283, 19864, 10.1074/jbc.M800798200

Zhang, 2011, Ovarian cancer-associated fibroblasts contribute to epithelial ovarian carcinoma metastasis by promoting angiogenesis, lymphangiogenesis and tumor cell invasion, Cancer Lett, 303, 47, 10.1016/j.canlet.2011.01.011

Friedl, 2003, Tumour-cell invasion and migration: Diversity and escape mechanisms, Nat Rev Cancer, 3, 362, 10.1038/nrc1075

Steeg, 2006, Tumor metastasis: Mechanistic insights and clinical challenges, Nat Med, 12, 895, 10.1038/nm1469

Valastyan, 2011, Tumor metastasis: Molecular insights and evolving paradigms, Cell, 147, 275, 10.1016/j.cell.2011.09.024

Liotta, 1977, Degradation of basement membrane by murine tumor cells, J Natl Cancer Inst, 58, 1427, 10.1093/jnci/58.5.1427

Liotta, 1986, Tumor invasion and metastases - role of the extracellular matrix: Rhoads memorial Award lecture, Cancer Res, 46, 1

Fingleton, 2001, Matrilysin [MMP-7] expression selects for cells with reduced sensitivity to apoptosis, Neoplasia, 3, 459, 10.1038/sj.neo.7900190

Noë, 2001, Release of an invasion promoter E-cadherin fragment by matrilysin and stromelysin-1, J Cell Sci, 114, 111, 10.1242/jcs.114.1.111

Sameni, 2003, Functional imaging of proteolysis: Stromal and inflammatory cells increase tumor proteolysis, Mol Imaging, 2, 159, 10.1162/153535003322556903

Grimshaw, 2004, A role for endothelin-2 and its receptors in breast tumor cell invasion, Cancer Res, 64, 2461, 10.1158/0008-5472.CAN-03-1069

Sahai, 2005, Mechanisms of cancer cell invasion, Curr Opin Genet Dev, 15, 87, 10.1016/j.gde.2004.12.002

Gaggioli, 2007, Fibroblast-led collective invasion of carcinoma cells with differing roles for RhoGTPases in leading and following cells, Nat Cell Biol, 9, 1392, 10.1038/ncb1658

Provenzano, 2006, Collagen reorganization at the tumor-stromal interface facilitates local invasion, BMC Med, 4, 38, 10.1186/1741-7015-4-38

Provenzano, 2008, Contact guidance mediated three-dimensional cell migration is regulated by rho/rock-dependent matrix reorganization, Biophys J, 95, 5374, 10.1529/biophysj.108.133116

Goetz, 2011, Biomechanical remodeling of the microenvironment by stromal caveolin-1 favors tumor invasion and metastasis, Cell, 146, 148, 10.1016/j.cell.2011.05.040

Chen, 2011, CCL18 from tumor-associated macrophages promotes breast cancer metastasis via PItPnm3, Cancer Cell, 19, 541, 10.1016/j.ccr.2011.02.006

Yamaguchi, 2006, Invadopodia and podosomes in tumor invasion, Eur J Cell Biol, 85, 213, 10.1016/j.ejcb.2005.10.004

Yamaguchi, 2005, Molecular mechanisms of invadopodium formation: The role of the N-WASP-Arp2/3 complex pathway and cofilin, J Cell Biol, 168, 441, 10.1083/jcb.200407076

Buccione, 2004, Foot and mouth: Podosomes, invadopodia and circular dorsal ruffles, Nat Rev Mol Cell Biol, 5, 647, 10.1038/nrm1436

Calle, 2004, Wiskott-Aldrich syndrome protein and the cytoskeletal dynamics of dendritic cells, J Pathol, 204, 460, 10.1002/path.1651

Linder, 2003, Podosomes: Adhesion hot-spots of invasive cells, Trends Cell Biol, 13, 376, 10.1016/S0962-8924(03)00128-4

Mizutani, 2002, Essential role of neural Wiskott-Aldrich syndrome protein in podosome formation and degradation of extracellular matrix in src-transformed fibroblasts, Cancer Res, 62, 669

Moreno-Bueno, 2008, Transcriptional regulation of cell polarity in EMT and cancer, Oncogene, 27, 6958, 10.1038/onc.2008.346

Thiery, 2002, Epithelial-mesenchymal transitions in tumour progression, Nat Rev Cancer, 2, 442, 10.1038/nrc822

Liu, 2013, FGFR4 promotes stroma-induced epithelial-to-mesenchymal transition in colorectal cancer, Cancer Res, 73, 5926, 10.1158/0008-5472.CAN-12-4718

Bergers, 2003, Benefits of targeting both pericytes and endothelial cells in the tumor vasculature with kinase inhibitors, J Clin Invest, 111, 1287, 10.1172/JCI200317929

Raza, 2010, Pericytes and vessel maturation during tumor angiogenesis and metastasis, Am J Hematol, 85, 593, 10.1002/ajh.21745

Cooke, 2012, Pericyte depletion results in hypoxia-associated epithelial-to-mesenchymal transition and metastasis mediated by met signaling pathway, Cancer Cell, 21, 66, 10.1016/j.ccr.2011.11.024

Cano, 2000, The transcription factor snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression, Nat Cell Biol, 2, 76, 10.1038/35000025

Batlle, 2000, The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells, Nat Cell Biol, 2, 84, 10.1038/35000034

Zhou, 2004, Dual regulation of Snail by GSK-3beta-mediated phosphorylation in control of epithelial-mesenchymal transition, Nat Cell Biol, 6, 931, 10.1038/ncb1173

Wu, 2009, Stabilization of snail by NF-kappaB is required for inflammation-induced cell migration and invasion, Cancer Cell, 15, 416, 10.1016/j.ccr.2009.03.016

Quigley, 1998, Tumor cell intravasation alucidated: The chick embryo opens the window, Cell, 94, 281, 10.1016/S0092-8674(00)81470-1

Wyckoff, 2000, A critical step in metastasis: In vivo analysis of intravasation at the primary tumor, Cancer Res, 60, 2504

Wolf, 2012, Endothelial CCR2 signaling induced by colon carcinoma cells enables extravasation via the JAK2-Stat5 and p38MAPk pathway, Cancer Cell, 22, 91, 10.1016/j.ccr.2012.05.023

Gay, 2011, Contribution of platelets to tumour metastasis, Nat Rev Cancer, 11, 123, 10.1038/nrc3004

Nagrath, 2007, Isolation of rare circulating tumour cells in cancer patients by microchip technology, Nature, 450, 1235, 10.1038/nature06385

Huang, 2013, Immunomagnetic nanoscreening of circulating tumor cells with a motion controlled microfluidic system, Biomed Microdevices, 15, 673, 10.1007/s10544-012-9718-8

Cai, 2013, 2-NBDG fluorescence imaging of hyper-metabolic circulating tumor cells in mouse xenograft model of breast cancer, J Fluoresc, 23, 213, 10.1007/s10895-012-1136-z

Nieswandt, 1999, Lysis of tumor cells by natural killer cells in mice is impeded by platelets, Cancer Res, 59, 1295

Mbeunkui, 2009, Cancer and the tumor micro-environment: A review of an essential relationship, Cancer Chemother Pharmacol, 63, 571, 10.1007/s00280-008-0881-9

Gupta, 2007, Mediators of vascular remodelling co-opted for sequential steps in lung metastasis, Nature, 446, 765, 10.1038/nature05760

Psaila, 2007, Priming the 'soil' for breast cancer metastasis: The pre-metastatic niche, Breast Dis, 26, 65, 10.3233/BD-2007-26106

Psaila, 2009, The metastatic niche: Adapting the foreign soil, Nat Rev Cancer, 9, 285, 10.1038/nrc2621

Hiratsuka, 2006, Tumour-mediated upregulation of chemoattractants and recruitment of myeloid cells predetermines lung metastasis, Nat Cell Biol, 8, 1369, 10.1038/ncb1507

Rafii, 2006, S100 chemokines mediate bookmarking of premetastatic niches, Nat Cell Biol, 8, 1321, 10.1038/ncb1206-1321

Hiratsuka, 2008, The S100A8-serum amyloid A3-TLR4 paracrine cascade establishes a pre-metastatic phase, Nat Cell Biol, 10, 1349, 10.1038/ncb1794

Kaplan, 2005, VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche, Nature, 438, 820, 10.1038/nature04186

Nakasone, 2012, Imaging tumor-stroma interactions during chemotherapy reveals contributions of the microenvironment to resistance, Cancer Cell, 21, 488, 10.1016/j.ccr.2012.02.017

Roodhart, 2011, Mesenchymal stem cells induce resistance to chemotherapy through the release of platinum-induced fatty acids, Cancer Cell, 20, 370, 10.1016/j.ccr.2011.08.010

Joosse, 2015, Tumor-educated platelets as liquid biopsy in cancer patients, Cancer Cell, 28, 552, 10.1016/j.ccell.2015.10.007

Wong, 2015, The Cancer Genome Atlas Analysis predicts microRNA for targeting cancer growth and vascularization in glioblastoma, Mol Ther, 23, 1234, 10.1038/mt.2015.72

Resnick, 2016, Analysis of tumor DNA in urine as a highly sensitive liquid biopsy for patients with non-muscle invasive bladder cancer (NMIBC), Clin Cancer Res, 22, 14, 10.1158/1557-3265.PMSCLINGEN15-14

Mishra, 2015, In Silico modeling-based identification of glucose transporter 4 (GLUT4)-selective inhibitors for cancer therapy, J Biol Chem, 290, 14441, 10.1074/jbc.M114.628826

Tuxhorn, 2002, Inhibition of transforming growth factor-beta activity decreases angiogenesis in a human prostate cancer-reactive stroma xenograft model, Cancer Res, 62, 6021

Carmeliet, 2003, Angiogenesis in health and disease, Nat Med, 9, 653, 10.1038/nm0603-653

Joyce, 2005, A functional heparan sulfate mimetic implicates both heparanase and heparan sulfate in tumor angiogenesis and invasion in a mouse model of multistage cancer, Oncogene, 24, 4037, 10.1038/sj.onc.1208602

Hamano, 2003, Physiological levels of tumstatin, a fragment of collagen IV alpha3 chain, are generated by MMP-9 proteolysis and suppress angiogenesis via alphav beta3 integrin, Cancer Cell, 3, 589, 10.1016/S1535-6108(03)00133-8

Rudland, 2002, Prognostic significance of the metastasis-associated protein osteopontin in human breast cancer, Cancer Res, 62, 3417

El-Tanani, 2006, The regulation and role of osteopontin in malignant transformation and cancer, Cytokine Growth Factor Rev, 17, 463, 10.1016/j.cytogfr.2006.09.010

Tuck, 2001, The role of osteopontin in breast cancer: Clinical and experimental studies, J Mammary Gland Biol Neoplasia, 6, 419, 10.1023/A:1014734930781

Weber, 2001, The metastasis gene osteopontin: A candidate target for cancer therapy, Biochim Biophys Acta, 1552, 61

Matarrese, 2000, Galectin-3 overexpression protects from apoptosis by improving cell adhesion properties, Int J Cancer, 85, 545, 10.1002/(SICI)1097-0215(20000215)85:4<545::AID-IJC17>3.0.CO;2-N

Inohara, 1999, Expression of galectin-3 in fine-needle aspirates as a diagnostic marker differentiating benign from malignant thyroid neoplasms, Cancer, 85, 2475, 10.1002/(SICI)1097-0142(19990601)85:11<2475::AID-CNCR25>3.0.CO;2-1

Pinedo, 1998, Involvement of platelets in tumour angiogenesis?, Lancet, 352, 1775, 10.1016/S0140-6736(98)05095-8

Pai, 2002, Prostaglandin E2 transactivates EGF receptor: A novel mechanism for promoting colon cancer growth and gastrointestinal hypertrophy, Nat Med, 8, 289, 10.1038/nm0302-289

Ikushima, 2010, TGFbeta signalling: A complex web in cancer progression, Nat Rev Cancer, 10, 415, 10.1038/nrc2853

Sierko, 2004, Platelets and angiogenesis in malignancy, Semin Thromb Hemost, 30, 95, 10.1055/s-2004-822974

Medina, 2010, Histamine receptors and cancer pharmacology, Br J Pharmacol, 161, 755, 10.1111/j.1476-5381.2010.00961.x

Moghaddam, 1995, Thymidine phosphorylase is angiogenic and promotes tumor growth, Proc Natl Acad Sci USA, 92, 998, 10.1073/pnas.92.4.998

Bronckaers, 2009, The dual role of thymidine phosphorylase in cancer development and chemotherapy, Med Res Rev, 29, 903, 10.1002/med.20159

Geiger, 2007, Critical role for TrkB kinase function in anoikis suppression, tumorigenesis, and metastasis, Cancer Res, 67, 6221, 10.1158/0008-5472.CAN-07-0121

Kim, 1998, P-selectin deficiency attenuates tumor growth and metastasis, Proc Natl Acad Sci USA, 95, 9325, 10.1073/pnas.95.16.9325

David, 2010, Cancer cell expression of autotaxin controls bone metastasis formation in mouse through lysophosphatidic acid-dependent activation of osteoclasts, PLoS One, 5, e9741, 10.1371/journal.pone.0009741

Visentin, 2006, Validation of an anti-sphingosine-1-phosphate antibody as a potential therapeutic in reducing growth, invasion, and angiogenesis in multiple tumor lineages, Cancer Cell, 9, 225, 10.1016/j.ccr.2006.02.023

Ruf, 2006, Thrombin generation and the pathogenesis of cancer, Semin Thromb Hemost, 32, 61, 10.1055/s-2006-939555

Bajou, 1998, Absence of host plasminogen activator inhibitor 1 prevents cancer invasion and vascularization, Nat Med, 4, 923, 10.1038/nm0898-923

Falcón, 2009, Contrasting actions of selective inhibitors of angiopoietin-1 and angiopoietin-2 on the normalization of tumor blood vessels, Am J Pathol, 175, 2159, 10.2353/ajpath.2009.090391

Payne, 2002, The role of chemokines in melanoma tumor growth and metastasis, J Invest Dermatol, 118, 915, 10.1046/j.1523-1747.2002.01725.x

Wu, 2008, CCL3-CCR5 axis regulates intratumoral accumulation of leukocytes and fibroblasts and promotes angiogenesis in murine lung metastasis process, J Immunol, 181, 6384, 10.4049/jimmunol.181.9.6384

Läubli, 2009, Selectin-mediated activation of endothelial cells induces expression of CCL5 and promotes metastasis through recruitment of monocytes, Blood, 114, 4583, 10.1182/blood-2008-10-186585

Yi, 2003, The CCL6 chemokine is differentially regulated by c-Myc and L-Myc, and promotes tumorigenesis and metastasis, Cancer Res, 63, 2923

Keeley, 2010, CXC chemokines in cancer angiogenesis and metastases, Adv Cancer Res, 106, 91, 10.1016/S0065-230X(10)06003-3

Nakamura, 2006, RANKL-induced CCL22/macrophage-derived chemokine produced from osteoclasts potentially promotes the bone metastasis of lung cancer expressing its receptor CCR4, Clin Exp Metastasis, 23, 9, 10.1007/s10585-006-9006-1

Romagnani, 2004, CXC chemokines: The regulatory link between inflammation and angiogenesis, Trends Immunol, 25, 201, 10.1016/j.it.2004.02.006

Strieter, 2005, CXC chemokines in angiogenesis, Cytokine Growth Factor Rev, 16, 593, 10.1016/j.cytogfr.2005.04.007

Feliciano, 2012, CXCL1 and CXCL2 link metastasis and chemoresistance, Nat Genet, 44, 840

Keane, 2004, Depletion of CXCR2 inhibits tumor growth and angiogenesis in a murine model of lung cancer, J Immunol, 172, 2853, 10.4049/jimmunol.172.5.2853

White, 2003, Macrophage migration inhibitory factor and CXC chemokine expression in non-small cell lung cancer: Role in angiogenesis and prognosis, Clin Cancer Res, 9, 853

Strieter, 2006, Cancer CXC chemokine networks and tumour angiogenesis, Eur J Cancer, 42, 768, 10.1016/j.ejca.2006.01.006

Miyazaki, 2006, Down-regulation of CXCL5 inhibits squamous carcinogenesis, Cancer Res, 66, 4279, 10.1158/0008-5472.CAN-05-4398

Gijsbers, 2005, GCP-2/CXCL6 synergizes with other endothelial cell-derived chemokines in neutrophil mobilization and is associated with angiogenesis in gastrointestinal tumors, Exp Cell Res, 303, 331, 10.1016/j.yexcr.2004.09.027

Verbeke, 2011, Isotypic neutralizing antibodies against mouse GCP-2/CXCL6 inhibit melanoma growth and metastasis, Cancer Lett, 302, 54, 10.1016/j.canlet.2010.12.013

Tang, 2008, Increased invasion through basement membrane by CXCL7-transfected breast cells, Am J Surg, 196, 690, 10.1016/j.amjsurg.2008.08.001

Bachelder, 2002, Vascular endothelial growth factor promotes breast carcinoma invasion in an autocrine manner by regulating the chemokine receptor CXCR4, Cancer Res, 62, 7203

Belperio, 2004, The SDF-1/CXCL 12/CXCR4 biological axis in non-small cell lung cancer metastases, Chest, 125, 156S, 10.1378/chest.125.5_suppl.156S

Pan, 2006, Stromal derived factor-1 (SDF-1/CXCL12) and cXcr4 in renal cell carcinoma metastasis, Mol Cancer, 5, 56, 10.1186/1476-4598-5-56