Therapeutic Targeting of Hyaluronan in the Tumor Stroma

Sund, 2009, Tumor stroma derived biomarkers in cancer, Cancer Metastasis Rev., 28, 177, 10.1007/s10555-008-9175-2

Weinberg, 2008, Coevolution in the tumor microenvironment, Nat. Genet., 40, 494, 10.1038/ng0508-494

Shimoda, 2010, Carcinoma-associated fibroblasts are a rate-limiting determinant for tumour progression, Semin. Cell Dev. Biol., 21, 19, 10.1016/j.semcdb.2009.10.002

Johansson, 2012, Remodeling of tumor stroma and response to therapy, Cancers, 4, 340, 10.3390/cancers4020340

Bissell, 2011, Why don’t we get more cancer? A proposed role of the microenvironment in restraining cancer progression, Nat. Med., 17, 320, 10.1038/nm.2328

Shepard, 2008, Signal integration: A framework for understanding the efficacy of therapeutics targeting the human EGFR family, J. Clin. Invest., 118, 3574, 10.1172/JCI36049

Ferrara, 2005, VEGF as a therapeutic target in cancer, Oncology, 69, 11, 10.1159/000088479

Kelleher, 2011, Hedgehog signaling and therapeutics in pancreatic cancer, Carcinogenesis, 32, 445, 10.1093/carcin/bgq280

Liu, 2012, TH-302, a hypoxia-activated prodrug with broad in vivo preclinical combination therapy efficacy: Optimization of dosing regimens and schedules, Cancer Chemother. Pharmacol., 69, 1487, 10.1007/s00280-012-1852-8

Weiss, 2011, Phase 1 study of the safety, tolerability, and pharmacokinetics of TH-302, a hypoxia-activated prodrug, in patients with advanced solid malignancies, Clin. Cancer Res., 17, 2997, 10.1158/1078-0432.CCR-10-3425

Jacobetz, M.A., Chan, D.S., Neesse, A., Bapiro, T.E., Cook, N., Frese, K.K., Feig, C., Nakagawa, T., Caldwell, M.E., and Zecchini, H.I. (2012). Hyaluronan impairs vascular function and drug delivery in a mouse model of pancreatic cancer. Gut.

Provenzano, 2012, Enzymatic targeting of the stroma ablates physical barriers to treatment of pancreatic ductal adenocarcinoma, Cancer Cell, 21, 418, 10.1016/j.ccr.2012.01.007

Jiang, 2012, Effective targeting of the tumor microenvironment for cancer therapy, Anticancer Res., 32, 1203

Thompson, 2010, Enzymatic depletion of tumor hyaluronan induces antitumor responses in preclinical animal models, Mol. Cancer Ther., 9, 3052, 10.1158/1535-7163.MCT-10-0470

Phase 1 Study of PEGPH20 With Initial Dexamethasone Premedication Given Intravenously to Patients With Advanced Solid Tumors (Sponsor: Halozyme Therapeutics). Available online:http://clinicaltrials.gov/ct2/show/NCT01170897?term=NCT01170897&rank=1/.

Phase 1B/2 Study of Gemcitabine + PEGPH20 versus Gemcitabine Alone in Stage IV Previously Untreated Pancreatic Cancer (Sponsor: Halozyme Therapeutics). Available online:http://clinicaltrials.gov/ct2/show/NCT01453153?term=NCT01453153&rank=1/.

Weigel, 2007, Hyaluronan synthases: A decade-plus of novel glycosyltransferases, J. Biol. Chem., 282, 36777, 10.1074/jbc.R700036200

Jokela, 2011, Cellular content of UDP-N-acetylhexosamines controls hyaluronan synthase 2 expression and correlates with O-linked N-acetylglucosamine modification of transcription factors YY1 and SP1, J. Biol. Chem., 286, 33632, 10.1074/jbc.M111.265637

Itano, 1999, Three isoforms of mammalian hyaluronan synthases have distinct enzymatic properties, J. Biol. Chem., 274, 25085, 10.1074/jbc.274.35.25085

Viola, 2008, Molecular control of the hyaluronan biosynthesis, Connect. Tissue Res., 49, 111, 10.1080/03008200802148405

Li, 2007, Growth factor regulation of hyaluronan synthesis and degradation in human dermal fibroblasts: Importance of hyaluronan for the mitogenic response of PDGF-BB, Biochem. J., 404, 327, 10.1042/BJ20061757

Wilkinson, 2006, Overexpression of hyaluronan synthases alters vascular smooth muscle cell phenotype and promotes monocyte adhesion, J. Cell. Physiol., 206, 378, 10.1002/jcp.20468

Camenisch, 2000, Disruption of hyaluronan synthase-2 abrogates normal cardiac morphogenesis and hyaluronan-mediated transformation of epithelium to mesenchyme, J. Clin. Invest., 106, 349, 10.1172/JCI10272

Tien, 2005, Three vertebrate hyaluronan synthases are expressed during mouse development in distinct spatial and temporal patterns, Dev. Dyn., 233, 130, 10.1002/dvdy.20328

Jokela, T. (2011). Regulation of hyaluronan synthesis by UDP-sugars. [Ph.D. Thesis, University of Eastern Finland].

Toole, 2004, Hyaluronan: From extracellular glue to pericellular cue, Nat. Rev. Cancer, 4, 528, 10.1038/nrc1391

Spicer, 2004, Hyaluronan and morphogenesis, Birth Defects Res. C Embryo Today, 72, 89, 10.1002/bdrc.20006

Spicer, 2002, Investigation of hyaluronan function in the mouse through targeted mutagenesis, Glycoconj. J., 19, 341, 10.1023/A:1025321105691

Koyama, 2007, Hyperproduction of hyaluronan in neu-induced mammary tumor accelerates angiogenesis through stromal cell recruitment: Possible involvement of versican/PG-M, Am. J. Pathol., 170, 1086, 10.2353/ajpath.2007.060793

Csoka, 2001, The six hyaluronidase-like genes in the human and mouse genomes, Matrix Biol., 20, 499, 10.1016/S0945-053X(01)00172-X

Jadin, 2008, Skeletal and hematological anomalies in HYAL2-deficient mice: A second type of mucopolysaccharidosis IX?, FASEB J., 22, 4316, 10.1096/fj.08-111997

Atmuri, 2008, Hyaluronidase 3 (HYAL3) knockout mice do not display evidence of hyaluronan accumulation, Matrix Biol., 27, 653, 10.1016/j.matbio.2008.07.006

Martin, 2008, A mouse model of human mucopolysaccharidosis IX exhibits osteoarthritis, Hum. Mol. Genet., 17, 1904, 10.1093/hmg/ddn088

Kimura, 2009, Functional roles of mouse sperm hyaluronidases, HYAL5 and SPAM1, in fertilization, Biol. Reprod., 81, 939, 10.1095/biolreprod.109.078816

Salo, 1999, Mutations in HYAL1, a member of a tandemly distributed multigene family encoding disparate hyaluronidase activities, cause a newly described lysosomal disorder, mucopolysaccharidosis IX, Proc. Natl. Acad. Sci. USA, 96, 6296, 10.1073/pnas.96.11.6296

Baba, 2002, Mouse sperm lacking cell surface hyaluronidase PH-20 can pass through the layer of cumulus cells and fertilize the egg, J. Biol. Chem., 277, 30310, 10.1074/jbc.M204596200

Wynne, C., Harvey, V., Schwabe, C., Waaka, D., McIntyre, C., and Bittner, B. (2012). Comparison of subcutaneous and intravenous administration of trastuzumab: A phase I/Ib trial in healthy male volunteers and patients With HER2-positive breast cancer. J. Clin. Pharmacol.

Frost, 2007, Recombinant human hyaluronidase (rHuPH20): An enabling platform for subcutaneous drug and fluid administration, Expert Opin. Drug Deliv., 4, 427, 10.1517/17425247.4.4.427

Bookbinder, 2006, A recombinant human enzyme for enhanced interstitial transport of therapeutics, J. Control. Release, 114, 230, 10.1016/j.jconrel.2006.05.027

Dea, 1973, Hyaluronic acid: A novel, double helical molecule, Science, 179, 560, 10.1126/science.179.4073.560

Tammi, 2008, Hyaluronan in human tumors: Pathobiological and prognostic messages from cell-associated and stromal hyaluronan, Semin. Cancer Biol., 18, 288, 10.1016/j.semcancer.2008.03.005

Simpson, 2008, Hyaluronan and hyaluronidase in genitourinary tumors, Front. Biosci., 13, 5664, 10.2741/3108

Itano, 2008, Altered hyaluronan biosynthesis in cancer progression, Semin. Cancer Biol., 18, 268, 10.1016/j.semcancer.2008.03.006

Erickson, 2012, Chain gangs: New aspects of hyaluronan metabolism, Biochem. Res. Int., 2012, 893947:1, 10.1155/2012/893947

Meyer, 1983, Macromolecular basis of globular protein exclusion and of swelling pressure in loose connective tissue (umbilical cord), Biochim. Biophys. Acta, 755, 388, 10.1016/0304-4165(83)90242-8

Jain, 2001, Delivery of molecular medicine to solid tumors: Lessons from in vivo imaging of gene expression and function, J. Control. Release, 74, 7, 10.1016/S0168-3659(01)00306-6

Jacobson, 2003, Hyaluronan content in experimental carcinoma is not correlated to interstitial fluid pressure, Biochem. Biophys. Res. Commun., 305, 1017, 10.1016/S0006-291X(03)00872-6

Tse, 2012, Mechanical compression drives cancer cells toward invasive phenotype, Proc. Natl. Acad. Sci. USA, 109, 911, 10.1073/pnas.1118910109

Wang, 2011, Akt directly regulates focal adhesion kinase through association and serine phosphorylation: Implication for pressure-induced colon cancer metastasis, Am. J. Physiol. Cell Physiol., 300, C657, 10.1152/ajpcell.00377.2010

Toole, 1990, Hyaluronan and its binding proteins, the hyaladherins, Curr. Opin. Cell Biol., 2, 839, 10.1016/0955-0674(90)90081-O

Day, 1999, The structure and regulation of hyaluronan-binding proteins, Biochem. Soc. Trans., 27, 115, 10.1042/bst0270115

Toole, 2000, Hyaluronan is not just a goo!, J. Clin. Invest., 106, 335, 10.1172/JCI10706

Varga, 2012, Brevican, neurocan, tenascin-C and versican are mainly responsible for the invasiveness of low-grade astrocytoma, Pathol. Oncol. Res., 18, 413, 10.1007/s12253-011-9461-0

Kodama, 2007, Versican expression in human cervical cancer, Eur. J. Cancer, 43, 1460, 10.1016/j.ejca.2007.02.007

Pukkila, 2007, High stromal versican expression predicts unfavourable outcome in oral squamous cell carcinoma, J. Clin. Pathol., 60, 267, 10.1136/jcp.2005.034181

Said, 2012, RhoGDI2 suppresses lung metastasis in mice by reducing tumor versican expression and macrophage infiltration, J. Clin. Invest., 122, 1503, 10.1172/JCI61392

Wu, 2005, The interaction of versican with its binding partners, Cell Res., 15, 483, 10.1038/sj.cr.7290318

Aspberg, 1997, The C-type lectin domains of lecticans, a family of aggregating chondroitin sulfate proteoglycans, bind tenascin-R by protein-protein interactions independent of carbohydrate moiety, Proc. Natl. Acad. Sci. USA, 94, 10116, 10.1073/pnas.94.19.10116

Aspberg, 1999, Fibulin-1 is a ligand for the C-type lectin domains of aggrecan and versican, J. Biol. Chem., 274, 20444, 10.1074/jbc.274.29.20444

Olin, 2001, The proteoglycans aggrecan and Versican form networks with fibulin-2 through their lectin domain binding, J. Biol. Chem., 276, 1253, 10.1074/jbc.M006783200

Yamagata, 1986, Chondroitin sulfate proteoglycan (PG-M-like proteoglycan) is involved in the binding of hyaluronic acid to cellular fibronectin, J. Biol. Chem., 261, 13526, 10.1016/S0021-9258(18)67050-4

Isogai, 2002, Versican interacts with fibrillin-1 and links extracellular microfibrils to other connective tissue networks, J. Biol. Chem., 277, 4565, 10.1074/jbc.M110583200

Mjaatvedt, 1998, The Cspg2 gene, disrupted in the hdf mutant, is required for right cardiac chamber and endocardial cushion formation, Dev. Biol., 202, 56, 10.1006/dbio.1998.9001

Huang, 1993, A serum-derived hyaluronan-associated protein (SHAP) is the heavy chain of the inter alpha-trypsin inhibitor, J. Biol. Chem., 268, 26725, 10.1016/S0021-9258(19)74373-7

Milner, 2007, The molecular basis of inter-alpha-inhibitor heavy chain transfer on to hyaluronan, Biochem. Soc. Trans., 35, 672, 10.1042/BST0350672

Yabushita, 2011, Clinicopathological role of serum-derived hyaluronan-associated protein (SHAP)-hyaluronan complex in endometrial cancer, Obstet. Gynecol. Int., 2011, 739150:1, 10.1155/2011/739150

Salustri, 2004, PTX3 plays a key role in the organization of the cumulus oophorus extracellular matrix and in in vivo fertilization, Development, 131, 1577, 10.1242/dev.01056

Kuznetsova, 2005, The N-terminal module of thrombospondin-1 interacts with the link domain of TSG-6 and enhances its covalent association with the heavy chains of inter-alpha-trypsin inhibitor, J. Biol. Chem., 280, 30899, 10.1074/jbc.M500701200

Kultti, 2006, Hyaluronan synthesis induces microvillus-like cell surface protrusions, J. Biol. Chem., 281, 15821, 10.1074/jbc.M512840200

Rilla, 2008, Pericellular hyaluronan coat visualized in live cells with a fluorescent probe is scaffolded by plasma membrane protrusions, J. Histochem. Cytochem., 56, 901, 10.1369/jhc.2008.951665

Misra, 2006, Hyaluronan constitutively regulates activation of multiple receptor tyrosine kinases in epithelial and carcinoma cells, J. Biol. Chem., 281, 34936, 10.1074/jbc.C600138200

Toole, 2009, Hyaluronan-CD44 interactions in cancer: Paradoxes and possibilities, Clin. Cancer Res., 15, 7462, 10.1158/1078-0432.CCR-09-0479

Bennett, 1995, Regulation of CD44 binding to hyaluronan by glycosylation of variably spliced exons, J. Cell Biol., 131, 1623, 10.1083/jcb.131.6.1623

Thankamony, 2006, Acylation of CD44 and its association with lipid rafts are required for receptor and hyaluronan endocytosis, J. Biol. Chem., 281, 34601, 10.1074/jbc.M601530200

Bourguignon, 2008, Hyaluronan-mediated CD44 activation of RhoGTPase signaling and cytoskeleton function promotes tumor progression, Semin. Cancer Biol., 18, 251, 10.1016/j.semcancer.2008.03.007

Stern, R. (2009). Hyaluronan in Cancer Biology, Academic Press/Elsevier. [1st].

Toole, 2008, Hyaluronan, CD44 and Emmprin: Partners in cancer cell chemoresistance, Drug Resist. Updat., 11, 110, 10.1016/j.drup.2008.04.002

Bourguignon, 1992, A CD44-like endothelial cell transmembrane glycoprotein (GP116) interacts with extracellular matrix and ankyrin, Mol. Cell. Biol., 12, 4464

Tsukita, 1994, ERM family members as molecular linkers between the cell surface glycoprotein CD44 and actin-based cytoskeletons, J. Cell Biol., 126, 391, 10.1083/jcb.126.2.391

Maxwell, 2008, Cell-surface and mitotic-spindle RHAMM: moonlighting or dual oncogenic functions?, J. Cell Sci., 121, 925, 10.1242/jcs.022038

Hall, 1994, Hyaluronan and the hyaluronan receptor RHAMM promote focal adhesion turnover and transient tyrosine kinase activity, J. Cell Biol., 126, 575, 10.1083/jcb.126.2.575

Hall, 2002, Src−/− fibroblasts are defective in their ability to disassemble focal adhesions in response to phorbol ester/hyaluronan treatment, Cell Commun. Adhes., 9, 273, 10.1080/15419060216306

Itano, 2004, Selective expression and functional characteristics of three mammalian hyaluronan synthases in oncogenic malignant transformation, J. Biol. Chem., 279, 18679, 10.1074/jbc.M313178200

Maxwell, 2003, RHAMM is a centrosomal protein that interacts with dynein and maintains spindle pole stability, Mol. Biol. Cell, 14, 2262, 10.1091/mbc.e02-07-0377

Tolg, 2010, RHAMM promotes interphase microtubule instability and mitotic spindle integrity through MEK1/ERK1/2 activity, J. Biol. Chem., 285, 26461, 10.1074/jbc.M110.121491

Joukov, 2006, The BRCA1/BARD1 heterodimer modulates ran-dependent mitotic spindle assembly, Cell, 127, 539, 10.1016/j.cell.2006.08.053

Maxwell, 2011, Interplay between BRCA1 and RHAMM regulates epithelial apicobasal polarization and may influence risk of breast cancer, PLoS Biol., 9, e1001199, 10.1371/journal.pbio.1001199

Pujana, 2007, Network modeling links breast cancer susceptibility and centrosome dysfunction, Nat. Genet., 39, 1338, 10.1038/ng.2007.2

Hamilton, 2007, The hyaluronan receptors CD44 and Rhamm (CD168) form complexes with ERK1,2 that sustain high basal motility in breast cancer cells, J. Biol. Chem., 282, 16667, 10.1074/jbc.M702078200

Jiang, 2005, Regulation of lung injury and repair by Toll-like receptors and hyaluronan, Nat. Med., 11, 1173, 10.1038/nm1315

Jiang, 2011, Hyaluronan as an immune regulator in human diseases, Physiol. Rev., 91, 221, 10.1152/physrev.00052.2009

Termeer, 2002, Oligosaccharides of Hyaluronan activate dendritic cells via toll-like receptor 4, J. Exp. Med., 195, 99, 10.1084/jem.20001858

Kouvidi, 2011, Role of receptor for hyaluronic acid-mediated motility (RHAMM) in low molecular weight hyaluronan (LMWHA)-mediated fibrosarcoma cell adhesion, J. Biol. Chem., 286, 38509, 10.1074/jbc.M111.275875

Gao, 2008, Hyaluronan oligosaccharides are potential stimulators to angiogenesis via RHAMM mediated signal pathway in wound healing, Clin. Invest. Med., 31, E106, 10.25011/cim.v31i3.3467

Lokeshwar, 2000, Differences in hyaluronic acid-mediated functions and signaling in arterial, microvessel, and vein-derived human endothelial cells, J. Biol. Chem., 275, 27641, 10.1074/jbc.M003084200

Wang, 2009, Ligation of TLR2 by versican: A link between inflammation and metastasis, Arch. Med. Res., 40, 321, 10.1016/j.arcmed.2009.04.005

Critchley, 2004, Cytoskeletal proteins talin and vinculin in integrin-mediated adhesion, Biochem. Soc. Trans., 32, 831, 10.1042/BST0320831

Hirose, 2012, Inhibition of Stabilin-2 elevates circulating hyaluronic acid levels and prevents tumor metastasis, Proc. Natl. Acad. Sci. USA, 109, 4263, 10.1073/pnas.1117560109

Chen, 2009, Increased expression of hyaluronic acid binding protein 1 is correlated with poor prognosis in patients with breast cancer, J. Surg. Oncol., 100, 382, 10.1002/jso.21329

Kim, 2011, Cell-surface receptor for complement component C1q (gC1qR) is a key regulator for lamellipodia formation and cancer metastasis, J. Biol. Chem., 286, 23093, 10.1074/jbc.M111.233304

Truedsson, 1951, A case of mesothelioma of the pleura and peritoneum producing hyaluronic acid, Acta Soc. Med. Ups., 56, 39

Jensen, 1954, Hyaluronic acid. IV. Isolation of hyaluronic acid from pseudomucinous ovarian cysts, Acta Pharmacol. Toxicol. (Copenh.), 10, 83, 10.1111/j.1600-0773.1954.tb01324.x

Pillwein, 1998, Hyaluronidase additional to standard chemotherapy improves outcome for children with malignant brain tumors, Cancer Lett., 131, 101, 10.1016/S0304-3835(98)00205-5

Baumgartner, 1998, The impact of extracellular matrix on the chemoresistance of solid tumors—Experimental and clinical results of hyaluronidase as additive to cytostatic chemotherapy, Cancer Lett., 131, 85, 10.1016/S0304-3835(98)00204-3

Klocker, 1998, Hyaluronidase as additive to induction chemotherapy in advanced squamous cell carcinoma of the head and neck, Cancer Lett., 131, 113, 10.1016/S0304-3835(98)00207-9

Spruss, 1995, Hyaluronidase significantly enhances the efficacy of regional vinblastine chemotherapy of malignant melanoma, J. Cancer Res. Clin. Oncol., 121, 193, 10.1007/BF01366962

Brekken, 1998, Hyaluronidase reduces the interstitial fluid pressure in solid tumours in a non-linear concentration-dependent manner, Cancer Lett., 131, 65, 10.1016/S0304-3835(98)00202-X

Eikenes, 2005, Hyaluronidase induces a transcapillary pressure gradient and improves the distribution and uptake of liposomal doxorubicin (Caelyx) in human osteosarcoma xenografts, Br. J. Cancer, 93, 81, 10.1038/sj.bjc.6602626

Kosaki, 1999, Overproduction of hyaluronan by expression of the hyaluronan synthase Has2 enhances anchorage-independent growth and tumorigenicity, Cancer Res., 59, 1141

Koyama, 2008, Significance of tumor-associated stroma in promotion of intratumoral lymphangiogenesis: Pivotal role of a hyaluronan-rich tumor microenvironment, Am. J. Pathol., 172, 179, 10.2353/ajpath.2008.070360

Shuster, 2002, Hyaluronidase reduces human breast cancer xenografts in SCID mice, Int. J. Cancer, 102, 192, 10.1002/ijc.10668

Simpson, 2002, Inhibition of prostate tumor cell hyaluronan synthesis impairs subcutaneous growth and vascularization in immunocompromised mice, Am. J. Pathol., 161, 849, 10.1016/S0002-9440(10)64245-9

Kim, 2004, Hyaluronan facilitates invasion of colon carcinoma cells in vitro via interaction with CD44, Cancer Res., 64, 4569, 10.1158/0008-5472.CAN-04-0202

Nishida, 2005, Antisense inhibition of hyaluronan synthase-2 in human osteosarcoma cells inhibits hyaluronan retention and tumorigenicity, Exp. Cell Res., 307, 194, 10.1016/j.yexcr.2005.03.026

Udabage, 2005, The over-expression of HAS2, Hyal-2 and CD44 is implicated in the invasiveness of breast cancer, Exp. Cell Res., 310, 205, 10.1016/j.yexcr.2005.07.026

Kudo, 2004, Effect of a hyaluronan synthase suppressor, 4-methylumbelliferone, on B16F-10 melanoma cell adhesion and locomotion, Biochem. Biophys. Res. Commun., 321, 783, 10.1016/j.bbrc.2004.07.041

Urakawa, 2012, Inhibition of hyaluronan synthesis in breast cancer cells by 4-methylumbelliferone suppresses tumorigenicity in vitro and metastatic lesions of bone in vivo, Int. J. Cancer, 130, 454, 10.1002/ijc.26014

Kultti, 2009, 4-Methylumbelliferone inhibits hyaluronan synthesis by depletion of cellular UDP-glucuronic acid and downregulation of hyaluronan synthase 2 and 3, Exp. Cell Res., 315, 1914, 10.1016/j.yexcr.2009.03.002

Yoshihara, 2005, A hyaluronan synthase suppressor, 4-methylumbelliferone, inhibits liver metastasis of melanoma cells, FEBS Lett., 579, 2722, 10.1016/j.febslet.2005.03.079

Auvinen, 2000, Hyaluronan in peritumoral stroma and malignant cells associates with breast cancer spreading and predicts survival, Am. J. Pathol., 156, 529, 10.1016/S0002-9440(10)64757-8

Tammi, 1999, Hyaluronan expression in gastric cancer cells is associated with local and nodal spread and reduced survival rate, Br. J. Cancer, 79, 1133, 10.1038/sj.bjc.6690180

Ropponen, 1998, Tumor cell-associated hyaluronan as an unfavorable prognostic factor in colorectal cancer, Cancer Res., 58, 342

Anttila, 2000, High levels of stromal hyaluronan predict poor disease outcome in epithelial ovarian cancer, Cancer Res., 60, 150

Josefsson, 2011, Prostate cancer increases hyaluronan in surrounding nonmalignant stroma, and this response is associated with tumor growth and an unfavorable outcome, Am. J. Pathol., 179, 1961, 10.1016/j.ajpath.2011.06.005

Kramer, 2011, Association of hyaluronic acid family members (HAS1, HAS2, and HYAL-1) with bladder cancer diagnosis and prognosis, Cancer, 117, 1197, 10.1002/cncr.25565

Pirinen, 2001, Prognostic value of hyaluronan expression in non-small-cell lung cancer: Increased stromal expression indicates unfavorable outcome in patients with adenocarcinoma, Int. J. Cancer, 95, 12, 10.1002/1097-0215(20010120)95:1<12::AID-IJC1002>3.0.CO;2-E

Hertweck, 2011, CD44 in hematological neoplasias, Ann. Hematol., 90, 493, 10.1007/s00277-011-1161-z

Tzankov, 2011, In situ RHAMM protein expression in acute myeloid leukemia blasts suggests poor overall survival, Ann. Hematol., 90, 901, 10.1007/s00277-011-1159-6

Lugli, 2006, Overexpression of the receptor for hyaluronic acid mediated motility is an independent adverse prognostic factor in colorectal cancer, Mod. Pathol., 19, 1302, 10.1038/modpathol.3800648

Godar, 2008, Growth-inhibitory and tumor- suppressive functions of p53 depend on its repression of CD44 expression, Cell, 134, 62, 10.1016/j.cell.2008.06.006

Sohr, 2008, RHAMM is differentially expressed in the cell cycle and downregulated by the tumor suppressor p53, Cell Cycle, 7, 3448, 10.4161/cc.7.21.7014

Willenberg, 2012, Melanoma cells control HA synthesis in peritumoral fibroblasts via PDGF-AA and PDGF-CC: Impact on melanoma cell proliferation, J. Invest. Dermatol., 132, 385, 10.1038/jid.2011.325

Hingorani, 2005, Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice, Cancer Cell, 7, 469, 10.1016/j.ccr.2005.04.023

Olive, 2009, Inhibition of Hedgehog signaling enhances delivery of chemotherapy in a mouse model of pancreatic cancer, Science, 324, 1457, 10.1126/science.1171362

Beckenlehner, 1992, Hyaluronidase enhances the activity of adriamycin in breast cancer models in vitro and in vivo, J. Cancer Res. Clin. Oncol., 118, 591, 10.1007/BF01211802

Smith, 1997, Hyaluronidase enhances the therapeutic effect of vinblastine in intralesional treatment of Kaposi’s sarcoma. Military Medical Consortium for the Advancement of Retroviral Research (MMCARR), J. Am. Acad. Dermatol., 36, 239, 10.1016/S0190-9622(97)70288-3

Novak, 1999, Hyaluronidase-2 overexpression accelerates intracerebral but not subcutaneous tumor formation of murine astrocytoma cells, Cancer Res., 59, 6246

Tan, 2011, HYAL1 overexpression is correlated with the malignant behavior of human breast cancer, Int. J. Cancer, 128, 1303, 10.1002/ijc.25460

Lokeshwar, 1999, Identification of bladder tumor-derived hyaluronidase: Its similarity to HYAL1, Cancer Res., 59, 4464

Lokeshwar, 2001, Stromal and epithelial expression of tumor markers hyaluronic acid and HYAL1 hyaluronidase in prostate cancer, J. Biol. Chem., 276, 11922, 10.1074/jbc.M008432200

Benitez, 2011, Targeting hyaluronidase for cancer therapy: Antitumor activity of sulfated hyaluronic acid in prostate cancer cells, Cancer Res., 71, 4085, 10.1158/0008-5472.CAN-10-4610

Lokeshwar, 1996, Association of elevated levels of hyaluronidase, a matrix-degrading enzyme, with prostate cancer progression, Cancer Res., 56, 651

Droller, 1998, Tumor-derived hyaluronidase: A diagnostic urine marker for high-grade bladder cancer, J. Urol., 160, 619, 10.1016/S0022-5347(01)62975-6

Franzmann, 2003, Expression of tumor markers hyaluronic acid and hyaluronidase (HYAL1) in head and neck tumors, Int. J. Cancer, 106, 438, 10.1002/ijc.11252

Bertrand, 1997, Increased hyaluronidase levels in breast tumor metastases, Int. J. Cancer, 73, 327, 10.1002/(SICI)1097-0215(19971104)73:3<327::AID-IJC4>3.0.CO;2-1

Delpech, 2002, Hyaluronidase is more elevated in human brain metastases than in primary brain tumours, Anticancer Res., 22, 2423

Pham, 1997, Tumor-derived hyaluronidase: A diagnostic urine marker for high-grade bladder cancer, Cancer Res., 57, 778

Stern, 1991, Hyaluronidase levels in urine from Wilms’ tumor patients, J. Natl. Cancer Inst., 83, 1569, 10.1093/jnci/83.21.1569

Nykopp, 2009, Expression of hyaluronan synthases (HAS1-3) and hyaluronidases (HYAL1-2) in serous ovarian carcinomas: Inverse correlation between HYAL1 and hyaluronan content, BMC Cancer, 9, 143, 10.1186/1471-2407-9-143

Lokeshwar, 2008, Hyaluronidase: Both a tumor promoter and suppressor, Semin. Cancer Biol., 18, 281, 10.1016/j.semcancer.2008.03.008

Jacobson, 2002, Expression of hyaluronan synthase 2 or hyaluronidase 1 differentially affect the growth rate of transplantable colon carcinoma cell tumors, Int. J. Cancer, 102, 212, 10.1002/ijc.10683

Lokeshwar, 2005, HYAL1 hyaluronidase in prostate cancer: A tumor promoter and suppressor, Cancer Res., 65, 7782, 10.1158/0008-5472.CAN-05-1022

Camenisch, 2000, Hyaluronan: Is bigger better?, Am. J. Respir. Cell Mol. Biol., 23, 431, 10.1165/ajrcmb.23.4.f201

Deed, 1997, Early-response gene signalling is induced by angiogenic oligosaccharides of hyaluronan in endothelial cells. Inhibition by non-angiogenic, high-molecular-weight hyaluronan, Int. J. Cancer, 71, 251, 10.1002/(SICI)1097-0215(19970410)71:2<251::AID-IJC21>3.0.CO;2-J

Rooney, 1995, The role of hyaluronan in tumour neovascularization (review), Int. J. Cancer, 60, 632, 10.1002/ijc.2910600511

Gaffney, 2009, Oligosaccharides of hyaluronan induce angiogenesis through distinct CD44 and RHAMM-mediated signalling pathways involving Cdc2 and gamma-adducin, Int. J. Oncol., 35, 761

Rahmanian, 1997, Hyaluronan oligosaccharides induce tube formation of a brain endothelial cell line in vitro, Exp. Cell Res., 237, 223, 10.1006/excr.1997.3792

Rooney, 1993, Angiogenic oligosaccharides of hyaluronan enhance the production of collagens by endothelial cells, J. Cell Sci., 105, 213, 10.1242/jcs.105.1.213

Lokeshwar, 1997, Tumor-associated hyaluronic acid: A new sensitive and specific urine marker for bladder cancer, Cancer Res., 57, 773

Urakawa, 2012, Therapeutic potential of hyaluronan oligosaccharides for bone metastasis of breast cancer, J. Orthop. Res., 30, 662, 10.1002/jor.21557

Zeng, 1998, Inhibition of tumor growth in vivo by hyaluronan oligomers, Int. J. Cancer, 77, 396, 10.1002/(SICI)1097-0215(19980729)77:3<396::AID-IJC15>3.0.CO;2-6

Slomiany, 2009, Inhibition of functional hyaluronan-CD44 interactions in CD133-positive primary human ovarian carcinoma cells by small hyaluronan oligosaccharides, Clin. Cancer Res., 15, 7593, 10.1158/1078-0432.CCR-09-2317

Hosono, 2007, Hyaluronan oligosaccharides inhibit tumorigenicity of osteosarcoma cell lines MG-63 and LM-8 in vitro and in vivo via perturbation of hyaluronan-rich pericellular matrix of the cells, Am. J. Pathol., 171, 274, 10.2353/ajpath.2007.060828

Slomiany, 2009, Abrogating drug resistance in malignant peripheral nerve sheath tumors by disrupting hyaluronan-CD44 interactions with small hyaluronan oligosaccharides, Cancer Res., 69, 4992, 10.1158/0008-5472.CAN-09-0143

Ghatak, 2002, Hyaluronan oligosaccharides inhibit anchorage-independent growth of tumor cells by suppressing the phosphoinositide 3-kinase/Akt cell survival pathway, J. Biol. Chem., 277, 38013, 10.1074/jbc.M202404200

Misra, 2003, Regulation of multidrug resistance in cancer cells by hyaluronan, J. Biol. Chem., 278, 25285, 10.1074/jbc.C300173200

Stern, 2006, Hyaluronan fragments: An information-rich system, Eur. J. Cell Biol., 85, 699, 10.1016/j.ejcb.2006.05.009

Rembrink, 1997, Orthotopic implantation of human prostate cancer cell lines: A clinically relevant animal model for metastatic prostate cancer, Prostate, 31, 168, 10.1002/(SICI)1097-0045(19970515)31:3<168::AID-PROS4>3.0.CO;2-H

Cos, 1998, Influence of melatonin on invasive and metastatic properties of MCF-7 human breast cancer cells, Cancer Res., 58, 4383

Richter, 2012, The interaction between CD44 on tumour cells and hyaluronan under physiologic flow conditions: Implications for metastasis formation, Histochem. Cell Biol., 137, 687, 10.1007/s00418-012-0916-5

Stephenson, 1992, Metastatic model for human prostate cancer using orthotopic implantation in nude mice, J. Natl. Cancer Inst., 17, 951, 10.1093/jnci/84.12.951

Veiseh, 2011, Hyaluronan metabolism in remodeling extracellular matrix: Probes for imaging and therapy of breast cancer, Integr. Biol. (Camb.), 4, 304, 10.1039/c0ib00096e