Advertisement

Versican: Role in Cancer Tumorigenesis

  • Paul A. Keire
  • Inkyung Kang
  • Thomas N. WightEmail author
Chapter
Part of the Biology of Extracellular Matrix book series (BEM)

Abstract

Versican is an extracellular matrix proteoglycan that is expressed in a wide variety of cancers. Several cellular sources for versican have been identified in a multitude of cancers including tumor cells, stromal cells, myeloid cells, and lymphoid cells. Versican plays a role in five of the six hallmarks of cancer including proliferative signaling, evasion of growth suppressor signaling, promotion of tissue invasion and metastasis, angiogenesis, and resistance to cell death. Versican also interacts with growth factors and cytokines to modify their activity and involvement in the cancer response. The synthesis and accumulation of versican is regulated by similar pathways that regulate cancer progression, such as the canonical Wnt/β-catenin pathway and receptor tyrosine kinases. The expression and accumulation of versican are associated with poor prognosis, disease progression, metastasis, and chemoresistance. A detailed analysis of the role of versican in the disease course of leiomyosarcoma is provided here as an example of the importance of this extracellular matrix component in cancer pathogenesis. Collectively, our results and those from other groups suggest that versican could serve as a point of control in the management and treatment of many cancers.

Keywords

Versican Hyaluronan Extracellular matrix Proteoglycans Cancer Markers Metastasis Cell phenotype Elastin Leiomyosarcoma 

Abbreviations

ADAMTS

A disintegrin and metalloproteinase with a thrombospondin family

CAF

Cancer-associated fibroblast

CTLs

Cytotoxic T lymphocytes

DAMP

Danger-associated molecular pattern

ECM

Extracellular matrix

EGF

Epidermal growth factor

FAK

Focal adhesion kinase

α-GAG

α-Glycosaminoglycan

β-GAG

β-Glycosaminoglycan

HAS

Hyaluronan synthase

HYAL1

Hyaluronidase-1

LEFs

Lymphoid-enhancing factors

LMS

Leiomyosarcoma

LOX

Lysyl oxidase

MMP

Matrix metalloproteinase

PSCs

Pancreatic stellate cells

PSGL-1

P-selectin glycoprotein ligand-1

RHAMM

Hyaluronan-mediated motility receptor

αSMA+

Alpha smooth muscle actin positive

TAMs

Tumor-associated macrophages

TCFs

T-cell factors

TGFβ

Transforming growth factor beta

TLR2

Toll-like receptor 2

TNFα

Tumor necrosis factor α

TSP1

Thrombospondin-1

Notes

Acknowledgments

We acknowledge Pioneer Award funding from the Wilske Center for Translational Research at Virginia Mason Medical Center and the Benaroya Research Institute. Dr. Kang was supported by the Ann Ramsay-Jenkins and William M. Jenkins Fellowship for Matrix Biology. We thank Dr. Virginia M. Green for the careful editing and preparation of this manuscript.

References

  1. Ang LC, Zhang Y, Cao L, Yang BL, Young B, Kiani C, Lee V, Allan K, Yang BB (1999) Versican enhances locomotion of astrocytoma cells and reduces cell adhesion through its G1 domain. J Neuropathol Exp Neurol 58(6):597–605PubMedCrossRefGoogle Scholar
  2. Asplund A, Friden V, Stillemark-Billton P, Camejo G, Bondjers G (2011) Macrophages exposed to hypoxia secrete proteoglycans for which LDL has higher affinity. Atherosclerosis 215(1):77–81PubMedCrossRefGoogle Scholar
  3. Asplund A, Stillemark-Billton P, Larsson E, Rydberg EK, Moses J, Hulten LM, Fagerberg B, Camejo G, Bondjers G (2010) Hypoxic regulation of secreted proteoglycans in macrophages. Glycobiology 20(1):33–40PubMedCrossRefGoogle Scholar
  4. Bharadwaj AG, Rector K, Simpson MA (2007) Inducible hyaluronan production reveals differential effects on prostate tumor cell growth and tumor angiogenesis. J Biol Chem 282(28):20561–20572PubMedCrossRefGoogle Scholar
  5. Bhowmick NA, Chytil A, Plieth D, Gorska AE, Dumont N, Shappell S, Washington MK, Neilson EG, Moses HL (2004) TGF-beta signaling in fibroblasts modulates the oncogenic potential of adjacent epithelia. Science 303(5659):848–851PubMedCrossRefGoogle Scholar
  6. Bogels M, Braster R, Nijland PG, Gul N, van de Luijtgaarden W, Fijneman RJ, Meijer GA, Jimenez CR, Beelen RH, van Egmond M (2012) Carcinoma origin dictates differential skewing of monocyte function. Oncoimmunology 1(6):798–809PubMedPubMedCentralCrossRefGoogle Scholar
  7. Bouez C, Reynaud C, Noblesse E, Thepot A, Gleyzal C, Kanitakis J, Perrier E, Damour O, Sommer P (2006) The lysyl oxidase LOX is absent in basal and squamous cell carcinomas and its knockdown induces an invading phenotype in a skin equivalent model. Clin Cancer Res 12(5):1463–1469PubMedCrossRefGoogle Scholar
  8. Brown LF, Guidi AJ, Schnitt SJ, Van De Water L, Iruela-Arispe ML, Yeo TK, Tognazzi K, Dvorak HF (1999) Vascular stroma formation in carcinoma in situ, invasive carcinoma, and metastatic carcinoma of the breast. Clin Cancer Res 5(5):1041–1056PubMedGoogle Scholar
  9. Busek P, Balaziova E, Matrasova I, Hilser M, Tomas R, Syrucek M, Zemanova Z, Krepela E, Belacek J, Sedo A (2016) Fibroblast activation protein alpha is expressed by transformed and stromal cells and is associated with mesenchymal features in glioblastoma. Tumour Biol 37(10):13961–13971PubMedCrossRefGoogle Scholar
  10. Cai Y, Balli D, Ustiyan V, Fulford L, Hiller A, Misetic V, Zhang Y, Paluch AM, Waltz SE, Kasper S, Kalin TV (2013) Foxm1 expression in prostate epithelial cells is essential for prostate carcinogenesis. J Biol Chem 288(31):22527–22541PubMedPubMedCentralCrossRefGoogle Scholar
  11. Carvalho CR, Carvalheira JB, Lima MH, Zimmerman SF, Caperuto LC, Amanso A, Gasparetti AL, Meneghetti V, Zimmerman LF, Velloso LA, Saad MJ (2003) Novel signal transduction pathway for luteinizing hormone and its interaction with insulin: activation of Janus kinase/signal transducer and activator of transcription and phosphoinositol 3-kinase/Akt pathways. Endocrinology 144(2):638–647PubMedCrossRefGoogle Scholar
  12. Cattaruzza S, Schiappacassi M, Ljungberg-Rose A, Spessotto P, Perissinotto D, Morgelin M, Mucignat MT, Colombatti A, Perris R (2002) Distribution of PG-M/versican variants in human tissues and de novo expression of isoform V3 upon endothelial cell activation, migration, and neoangiogenesis in vitro. J Biol Chem 277(49):47626–47635PubMedCrossRefGoogle Scholar
  13. Chang MY, Chan CK, Braun KR, Green PS, O'Brien KD, Chait A, Day AJ, Wight TN (2012) Monocyte-to-macrophage differentiation: synthesis and secretion of a complex extracellular matrix. J Biol Chem 287(17):14122–14135PubMedPubMedCentralCrossRefGoogle Scholar
  14. Chang MY, Tanino Y, Vidova V, Kinsella MG, Chan CK, Johnson PY, Wight TN, Frevert CW (2014) A rapid increase in macrophage-derived versican and hyaluronan in infectious lung disease. Matrix Biol 34:1–12PubMedPubMedCentralCrossRefGoogle Scholar
  15. de la Motte CA, Hascall VC, Drazba J, Bandyopadhyay SK, Strong SA (2003) Mononuclear leukocytes bind to specific hyaluronan structures on colon mucosal smooth muscle cells treated with polyinosinic acid: polycytidylic acid: inter-a-trypsin inhibitor is crucial to structure and function. Am J Pathol 163(1):121–133PubMedPubMedCentralCrossRefGoogle Scholar
  16. de Lima CR, de Arimatea dos Santos JJ, Nazario AC, Michelacci YM (2012) Changes in glycosaminoglycans and proteoglycans of normal breast and fibroadenoma during the menstrual cycle. Biochim Biophys Acta 1820(7):1009–1019PubMedCrossRefGoogle Scholar
  17. Derynck R, Goeddel DV, Ullrich A, Gutterman JU, Williams RD, Bringman TS, Berger WH (1987) Synthesis of messenger RNAs for transforming growth factors alpha and beta and the epidermal growth factor receptor by human tumors. Cancer Res 47(3):707–712PubMedGoogle Scholar
  18. Driessen EM, Pinhancos SS, Schneider P, de Lorenzo P, Valsecchi MG, Pieters R, Stam RW (2016) Versican expression is an adverse prognostic factor in MLL-rearranged infant acute lymphoblastic leukaemia. Eur J Cancer 57:87–90PubMedCrossRefGoogle Scholar
  19. Du WW, Yang BB, Shatseva TA, Yang BL, Deng Z, Shan SW, Lee DY, Seth A, Yee AJ (2010) Versican G3 promotes mouse mammary tumor cell growth, migration, and metastasis by influencing EGF receptor signaling. PLoS One 5(11):e13828PubMedPubMedCentralCrossRefGoogle Scholar
  20. Du WW, Yang W, Yee AJ (2013) Roles of versican in cancer biology—tumorigenesis, progression and metastasis. Histol Histopathol 28(6):701–713PubMedGoogle Scholar
  21. Dutt S, Kleber M, Matasci M, Sommer L, Zimmermann DR (2006) Versican V0 and V1 guide migratory neural crest cells. J Biol Chem 281(17):12123–12131PubMedCrossRefGoogle Scholar
  22. Dvorak HF (1986) Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N Engl J Med 315(26):1650–1659PubMedCrossRefGoogle Scholar
  23. Dvorak HF (2002) Vascular permeability factor/vascular endothelial growth factor: a critical cytokine in tumor angiogenesis and a potential target for diagnosis and therapy. J Clin Oncol 20(21):4368–4380PubMedCrossRefGoogle Scholar
  24. Dvorak HF (2015) Tumors: wounds that do not heal-redux. Cancer Immunol Res 3(1):1–11PubMedPubMedCentralCrossRefGoogle Scholar
  25. Evanko SP, Potter-Perigo S, Bollyky PL, Nepom GT, Wight TN (2012) Hyaluronan and versican in the control of human T-lymphocyte adhesion and migration. Matrix Biol 31(2):90–100PubMedCrossRefGoogle Scholar
  26. Fanhchaksai K, Okada F, Nagai N, Pothacharoen P, Kongtawelert P, Hatano S, Makino S, Nakamura T, Watanabe H (2016) Host stromal versican is essential for cancer-associated fibroblast function to inhibit cancer growth. Int J Cancer 138(3):630–641PubMedCrossRefGoogle Scholar
  27. Feinberg RN, Beebe DC (1983) Hyaluronate in vasculogenesis. Science 220(4602):1177–1179PubMedCrossRefGoogle Scholar
  28. Folberg R, Arbieva Z, Moses J, Hayee A, Sandal T, Kadkol S, Lin AY, Valyi-Nagy K, Setty S, Leach L, Chevez-Barrios P, Larsen P, Majumdar D, Pe'er J, Maniotis AJ (2006) Tumor cell plasticity in uveal melanoma: microenvironment directed dampening of the invasive and metastatic genotype and phenotype accompanies the generation of vasculogenic mimicry patterns. Am J Pathol 169(4):1376–1389PubMedPubMedCentralCrossRefGoogle Scholar
  29. Frey H, Schroeder N, Manon-Jensen T, Iozzo RV, Schaefer L (2013) Biological interplay between proteoglycans and their innate immune receptors in inflammation. FEBS J 280(10):2165–2179PubMedPubMedCentralCrossRefGoogle Scholar
  30. Fu Y, Nagy JA, Brown LF, Shih SC, Johnson PY, Chan CK, Dvorak HF, Wight TN (2011) Proteolytic cleavage of versican and involvement of ADAMTS-1 in VEGF-A/VPF-induced pathological angiogenesis. J Histochem Cytochem 59(5):463–473PubMedPubMedCentralCrossRefGoogle Scholar
  31. Gao D, Joshi N, Choi H, Ryu S, Hahn M, Catena R, Sadik H, Argani P, Wagner P, Vahdat LT, Port JL, Stiles B, Sukumar S, Altorki NK, Rafii S, Mittal V (2012a) Myeloid progenitor cells in the premetastatic lung promote metastases by Inducing mesenchymal to epithelial transition. Cancer Res 72(6):1384–1394PubMedCrossRefGoogle Scholar
  32. Gao D, Vahdat LT, Wong S, Chang JC, Mittal V (2012b) Microenvironmental regulation of epithelial-mesenchymal transitions in cancer. Cancer Res 72(19):4883–4889PubMedPubMedCentralCrossRefGoogle Scholar
  33. Ghosh S, Albitar L, LeBaron R, Welch WR, Samimi G, Birrer MJ, Berkowitz RS, Mok SC (2010) Up-regulation of stromal versican expression in advanced stage serous ovarian cancer. Gynecol Oncol 119(1):114–120PubMedPubMedCentralCrossRefGoogle Scholar
  34. Grivennikov SI, Greten FR, Karin M (2010) Immunity, inflammation, and cancer. Cell 140(6):883–899PubMedPubMedCentralCrossRefGoogle Scholar
  35. Gupta N, Khan R, Kumar R, Kumar L, Sharma A (2015) Versican and its associated molecules: potential diagnostic markers for multiple myeloma. Clin Chim Acta 442:119–124PubMedCrossRefGoogle Scholar
  36. Gutmann DH (2015) Microglia in the tumor microenvironment: taking their TOLL on glioma biology. Neuro Oncol 17(2):171–173PubMedCrossRefGoogle Scholar
  37. Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100(1):57–70PubMedCrossRefGoogle Scholar
  38. Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144(5):646–674PubMedCrossRefGoogle Scholar
  39. Held-Feindt J, Paredes EB, Blomer U, Seidenbecher C, Stark AM, Mehdorn HM, Mentlein R (2006) Matrix-degrading proteases ADAMTS4 and ADAMTS5 (disintegrins and metalloproteinases with thrombospondin motifs 4 and 5) are expressed in human glioblastomas. Int J Cancer 118(1):55–61PubMedCrossRefGoogle Scholar
  40. Hirose J, Kawashima H, Yoshie O, Tashiro K, Miyasaka M (2001) Versican interacts with chemokines and modulates cellular responses. J Biol Chem 276(7):5228–5234PubMedCrossRefGoogle Scholar
  41. Hope C, Foulcer S, Jagodinsky J, Chen SX, Jensen JL, Patel S, Leith C, Maroulakou I, Callander N, Miyamoto S, Hematti P, Apte SS, Asimakopoulos F (2016) Immunoregulatory roles of versican proteolysis in the myeloma microenvironment. Blood 128(5):680–685PubMedPubMedCentralCrossRefGoogle Scholar
  42. Hope C, Ollar SJ, Heninger E, Hebron E, Jensen JL, Kim J, Maroulakou I, Miyamoto S, Leith C, Yang DT, Callander N, Hematti P, Chesi M, Bergsagel PL, Asimakopoulos F (2014) TPL2 kinase regulates the inflammatory milieu of the myeloma niche. Blood 123(21):3305–3315PubMedPubMedCentralCrossRefGoogle Scholar
  43. Hu F, a Dzaye OD, Hahn A, Yu Y, Scavetta RJ, Dittmar G, Kaczmarek AK, Dunning KR, Ricciardelli C, Rinnenthal JL, Heppner FL, Lehnardt S, Synowitz M, Wolf SA, Kettenmann H (2015) Glioma-derived versican promotes tumor expansion via glioma-associated microglial/macrophages Toll-like receptor 2 signaling. Neuro Oncol 17(2):200–210PubMedCrossRefGoogle Scholar
  44. Huang H, He X (2008) Wnt/beta-catenin signaling: new (and old) players and new insights. Curr Opin Cell Biol 20(2):119–125PubMedPubMedCentralCrossRefGoogle Scholar
  45. Iozzo RV (1995) Tumor stroma as a regulator of neoplastic behavior. Agonistic and antagonistic elements embedded in the same connective tissue. Lab Invest 73(2):157–160PubMedGoogle Scholar
  46. Iozzo RV, Bolender RP, Wight TN (1982) Proteoglycan changes in the intercellular matrix of human colon carcinoma: an integrated biochemical and stereologic analysis. Lab Invest 47(2):124–138PubMedGoogle Scholar
  47. Joyce JA, Fearon DT (2015) T cell exclusion, immune privilege, and the tumor microenvironment. Science 348(6230):74–80PubMedCrossRefGoogle Scholar
  48. Ju H, Lim B, Kim M, Noh SM, Han DS, HJ Y, Choi BY, Kim YS, Kim WH, Ihm C, Kang C (2010) Genetic variants A1826H and D2937Y in GAG-beta domain of versican influence susceptibility to intestinal-type gastric cancer. J Cancer Res Clin Oncol 136(2):195–201PubMedCrossRefGoogle Scholar
  49. Kähäri V-M, Larjava H, Uitto J (1991) Differential regulation of extracellular matrix proteoglycan (PG) gene expression. J Biol Chem 266:10609–10615Google Scholar
  50. Kang I, Barth JL, Sproul EP, Yoon DW, Braun KR, Argraves WS, Wight TN (2015) Expression of V3 versican by rat arterial smooth muscle cells promotes differentiated and anti-inflammatory phenotypes. J Biol Chem 290(35):21629–21641PubMedPubMedCentralCrossRefGoogle Scholar
  51. Kang I, Yoon DW, Braun KR, Wight TN (2014) Expression of versican V3 by arterial smooth muscle cells alters TGFβ-, EGF-, and NFkB-dependent signaling pathways, creating a microenvironment that resists monocyte adhesion. J Biol Chem 289(22):15393–15404PubMedPubMedCentralCrossRefGoogle Scholar
  52. Karvinen S, Kosma VM, Tammi MI, Tammi R (2003) Hyaluronan, CD44 and versican in epidermal keratinocyte tumours. Br J Dermatol 148(1):86–94PubMedCrossRefGoogle Scholar
  53. Keire PA, Bressler SL, Lemire JM, Edris B, Rubin BP, Rahmani M, McManus BM, van de Rijn M, Wight TN (2014) A role for versican in the development of leiomyosarcoma. J Biol Chem 289(49):34089–34103PubMedPubMedCentralCrossRefGoogle Scholar
  54. Keire PA, Bressler SL, Mulvihill ER, Starcher BC, Kang I, Wight TN (2016) Inhibition of versican expression by siRNA facilitates tropoelastin synthesis and elastic fiber formation by human SK-LMS-1 leiomyosarcoma smooth muscle cells in vitro and in vivo. Matrix Biol 50:67–81PubMedCrossRefGoogle Scholar
  55. Kenagy RD, Min SK, Clowes AW, Sandy JD (2009) Cell death-associated ADAMTS4 and versican degradation in vascular tissue. J Histochem Cytochem 57(9):889–897PubMedPubMedCentralCrossRefGoogle Scholar
  56. 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):102–106PubMedPubMedCentralCrossRefGoogle Scholar
  57. Kischel P, Waltregny D, Dumont B, Turtoi A, Greffe Y, Kirsch S, De Pauw E, Castronovo V (2010) Versican overexpression in human breast cancer lesions: known and new isoforms for stromal tumor targeting. Int J Cancer 126(3):640–650PubMedCrossRefGoogle Scholar
  58. Kitamura T, Qian BZ, Pollard JW (2015) Immune cell promotion of metastasis. Nat Rev Immunol 15(2):73–86PubMedPubMedCentralCrossRefGoogle Scholar
  59. Kobayashi H, Sugimoto H, Onishi S, Nakano K (2015) Novel biomarker candidates for the diagnosis of ovarian clear cell carcinoma. Oncol Lett 10(2):612–618PubMedPubMedCentralGoogle Scholar
  60. Kodama J, Hasengaowa, Kusumoto T, Seki N, Matsuo T, Nakamura K, Hongo A, Hiramatsu Y (2007a) Versican expression in human cervical cancer. Eur J Cancer 43(9):1460–1466PubMedCrossRefGoogle Scholar
  61. Kodama J, Hasengaowa, Kusumoto T, Seki N, Matsuo T, Ojima Y, Nakamura K, Hongo A, Hiramatsu Y (2007b) Prognostic significance of stromal versican expression in human endometrial cancer. Ann Oncol 18(2):269–274PubMedCrossRefGoogle Scholar
  62. Korswagen HC, Clevers HC (1999) Activation and repression of wingless/Wnt target genes by the TCF/LEF-1 family of transcription factors. Cold Spring Harb Symp Quant Biol 64:141–147PubMedCrossRefGoogle Scholar
  63. Koyama H, Hibi T, Isogai Z, Yoneda M, Fujimori M, Amano J, Kawakubo M, Kannagi R, Kimata K, Taniguchi S, Itano N (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(3):1086–1099PubMedPubMedCentralCrossRefGoogle Scholar
  64. Kreutziger KL, Muskheli V, Johnson P, Braun K, Wight TN, Murry CE (2011) Developing vasculature and stroma in engineered human myocardium. Tissue Eng Part A 17(9–10):1219–1228PubMedPubMedCentralCrossRefGoogle Scholar
  65. Kuznetsova SA, Issa P, Perruccio EM, Zeng B, Sipes JM, Ward Y, Seyfried NT, Fielder HL, Day AJ, Wight TN, Roberts DD (2006) Versican-thrombospondin-1 binding in vitro and colocalization in microfibrils induced by inflammation on vascular smooth muscle cells. J Cell Sci 119(Pt 21):4499–4509PubMedCrossRefGoogle Scholar
  66. Labropoulou VT, Theocharis AD, Ravazoula P, Perimenis P, Hjerpe A, Karamanos NK, Kalofonos HP (2006) Versican but not decorin accumulation is related to metastatic potential and neovascularization in testicular germ cell tumours. Histopathology 49(6):582–593PubMedCrossRefGoogle Scholar
  67. LaPierre DP, Lee DY, Li SZ, Xie YZ, Zhong L, Sheng W, Deng Z, Yang BB (2007) The ability of versican to simultaneously cause apoptotic resistance and sensitivity. Cancer Res 67(10):4742–4750PubMedCrossRefGoogle Scholar
  68. Lemire JM, Braun KR, Maurel P, Kaplan ED, Schwartz SM, Wight TN (1999) Versican/PG-M isoforms in vascular smooth muscle cells. Arterioscler Thromb Vasc Biol 19:1630–1639PubMedCrossRefGoogle Scholar
  69. Li D, Wang X, JL W, Quan WQ, Ma L, Yang F, KY W, Wan HY (2013) Tumor-produced versican V1 enhances hCAP18/LL-37 expression in macrophages through activation of TLR2 and vitamin D3 signaling to promote ovarian cancer progression in vitro. PLoS One 8(2):e56616PubMedPubMedCentralCrossRefGoogle Scholar
  70. Li F, Li S, Cheng T (2014) TGF-beta1 promotes osteosarcoma cell migration and invasion through the miR-143-versican pathway. Cell Physiol Biochem 34(6):2169–2179PubMedCrossRefGoogle Scholar
  71. Li Y, Li L, Brown TJ, Heldin P (2007) Silencing of hyaluronan synthase 2 suppresses the malignant phenotype of invasive breast cancer cells. Int J Cancer 120(12):2557–2567PubMedCrossRefGoogle Scholar
  72. Liu MF, Hu YY, Jin T, Xu K, Wang SH, Du GZ, Wu BL, Li LY, Xu LY, Li EM, Xu HX (2015) Matrix metalloproteinase-9/neutrophil gelatinase-associated lipocalin complex activity in human glioma samples predicts tumor presence and clinical prognosis. Dis Markers 2015:138974PubMedPubMedCentralGoogle Scholar
  73. Lo PH, Leung AC, Kwok CY, Cheung WS, Ko JM, Yang LC, Law S, Wang LD, Li J, Stanbridge EJ, Srivastava G, Tang JC, Tsao SW, Lung ML (2007) Identification of a tumor suppressive critical region mapping to 3p14.2 in esophageal squamous cell carcinoma and studies of a candidate tumor suppressor gene, ADAMTS9. Oncogene 26(1):148–157PubMedCrossRefGoogle Scholar
  74. Lo PH, Lung HL, Cheung AK, Apte SS, Chan KW, Kwong FM, Ko JM, Cheng Y, Law S, Srivastava G, Zabarovsky ER, Tsao SW, Tang JC, Stanbridge EJ, Lung ML (2010) Extracellular protease ADAMTS9 suppresses esophageal and nasopharyngeal carcinoma tumor formation by inhibiting angiogenesis. Cancer Res 70(13):5567–5576PubMedPubMedCentralCrossRefGoogle Scholar
  75. Lokeshwar VB, Cerwinka WH, Isoyama T, Lokeshwar BL (2005) HYAL1 hyaluronidase in prostate cancer: a tumor promoter and suppressor. Cancer Res 65(17):7782–7789PubMedCrossRefGoogle Scholar
  76. Malla N, Berg E, Theocharis AD, Svineng G, Uhlin-Hansen L, Winberg JO (2013) In vitro reconstitution of complexes between pro-matrix metalloproteinase-9 and the proteoglycans serglycin and versican. FEBS J 280(12):2870–2887PubMedCrossRefGoogle Scholar
  77. Marvel D, Gabrilovich DI (2015) Myeloid-derived suppressor cells in the tumor microenvironment: expect the unexpected. J Clin Invest 125(9):3356–3364PubMedPubMedCentralCrossRefGoogle Scholar
  78. Mattioni M, Soddu S, Prodosmo A, Visca P, Conti S, Alessandrini G, Facciolo F, Strigari L (2015) Prognostic role of serum p53 antibodies in lung cancer. BMC Cancer 15:148PubMedPubMedCentralCrossRefGoogle Scholar
  79. McMahon M, Ye S, Izzard L, Dlugolenski D, Tripp RA, Bean AG, McCulloch DR, Stambas J (2016) ADAMTS5 is a critical regulator of virus-specific T cell immunity. PLoS Biol 14(11):e1002580PubMedPubMedCentralCrossRefGoogle Scholar
  80. Miosge N, Sasaki T, Chu ML, Herken R, Timpl R (1998) Ultrastructural localization of microfibrillar fibulin-1 and fibulin-2 during heart development indicates a switch in molecular associations. Cell Mol Life Sci 54(6):606–613PubMedCrossRefGoogle Scholar
  81. Montesano R, Kumar S, Orci L, Pepper MS (1996) Synergistic effect of hyaluronan oligosaccharides and vascular endothelial growth factor on angiogenesis in vitro. Lab Invest 75(2):249–262PubMedGoogle Scholar
  82. Nara Y, Kato Y, Torii Y, Tsuji Y, Nakagaki S, Goto S, Isobe H, Nakashima N, Takeuchi J (1997) Immunohistochemical localization of extracellular matrix components in human breast tumours with special reference to PG-M/versican. Histochem J 29(1):21–30PubMedCrossRefGoogle Scholar
  83. Neesse A, Michl P, Frese KK, Feig C, Cook N, Jacobetz MA, Lolkema MP, Buchholz M, Olive KP, Gress TM, Tuveson DA (2011) Stromal biology and therapy in pancreatic cancer. Gut 60(6):861–868PubMedCrossRefGoogle Scholar
  84. Nikitovic D, Zafiropoulos A, Katonis P, Tsatsakis A, Theocharis AD, Karamanos NK, Tzanakakis GN (2006) Transforming growth factor-β as a key molecule triggering the expression of versican isoforms v0 and v1, hyaluronan synthase-2 and synthesis of hyaluronan in malignant osteosarcoma cells. IUBMB Life 58(1):47–53PubMedCrossRefGoogle Scholar
  85. Nishida Y, Knudson W, Knudson CB, Ishiguro N (2005) Antisense inhibition of hyaluronan synthase-2 in human osteosarcoma cells inhibits hyaluronan retention and tumorigenicity. Exp Cell Res 307(1):194–203PubMedPubMedCentralCrossRefGoogle Scholar
  86. Omary MB, Lugea A, Lowe AW, Pandol SJ (2007) The pancreatic stellate cell: a star on the rise in pancreatic diseases. J Clin Invest 117(1):50–59PubMedPubMedCentralCrossRefGoogle Scholar
  87. Onken J, Moeckel S, Leukel P, Leidgens V, Baumann F, Bogdahn U, Vollmann-Zwerenz A, Hau P (2014) Versican isoform V1 regulates proliferation and migration in high-grade gliomas. J Neurooncol 120(1):73–83PubMedCrossRefGoogle Scholar
  88. Ozdemir BC, Pentcheva-Hoang T, Carstens JL, Zheng X, Wu CC, Simpson TR, Laklai H, Sugimoto H, Kahlert C, Novitskiy SV, De Jesus-Acosta A, Sharma P, Heidari P, Mahmood U, Chin L, Moses HL, Weaver VM, Maitra A, Allison JP, LeBleu VS, Kalluri R (2014) Depletion of carcinoma-associated fibroblasts and fibrosis induces immunosuppression and accelerates pancreas cancer with reduced survival. Cancer Cell 25(6):719–734PubMedPubMedCentralCrossRefGoogle Scholar
  89. Pan S, Cheng L, White JT, Lu W, Utleg AG, Yan X, Urban ND, Drescher CW, Hood L, Lin B (2009) Quantitative proteomics analysis integrated with microarray data reveals that extracellular matrix proteins, catenins, and p53 binding protein 1 are important for chemotherapy response in ovarian cancers. OMICS 13(4):345–354PubMedCrossRefGoogle Scholar
  90. Papakonstantinou E, Dionyssopoulos A, Pesintzaki C, Minas A, Karakiulakis G (2003) Expression of proteoglycans and glycosaminoglycans in angiofibroma and fibrous plaque skin lesions from patients with tuberous sclerosis. Arch Dermatol Res 295(4):138–145PubMedCrossRefGoogle Scholar
  91. Perris R, Perissinotto D, Pettway Z, Bronner-Fraser M, Morgelin M, Kimata K (1996) Inhibitory effects of PG-H/aggrecan and PG-M/versican on avian neural crest cell migration. FASEB J 10(2):293–301PubMedGoogle Scholar
  92. Pirinen R, Leinonen T, Bohm J, Johansson R, Ropponen K, Kumpulainen E, Kosma VM (2005) Versican in nonsmall cell lung cancer: relation to hyaluronan, clinicopathologic factors, and prognosis. Hum Pathol 36(1):44–50PubMedCrossRefGoogle Scholar
  93. Potter-Perigo S, Johnson PY, Evanko SP, Chan CK, Braun KR, Wilkinson TS, Altman LC, Wight TN (2010) Polyinosine-polycytidylic acid stimulates versican accumulation in the extracellular matrix promoting monocyte adhesion. Am J Respir Cell Mol Biol 43(1):109–120PubMedCrossRefGoogle Scholar
  94. Preis M, Cohen T, Sarnatzki Y, Ben Yosef Y, Schneiderman J, Gluzman Z, Koren B, Lewis BS, Shaul Y, Flugelman MY (2006) Effects of fibulin-5 on attachment, adhesion, and proliferation of primary human endothelial cells. Biochem Biophys Res Commun 348(3):1024–1033PubMedCrossRefGoogle Scholar
  95. Pukkila M, Kosunen A, Ropponen K, Virtaniemi J, Kellokoski J, Kumpulainen E, Pirinen R, Nuutinen J, Johansson R, Kosma VM (2007) High stromal versican expression predicts unfavourable outcome in oral squamous cell carcinoma. J Clin Pathol 60(3):267–272PubMedCrossRefGoogle Scholar
  96. Pukkila MJ, Kosunen AS, Virtaniemi JA, Kumpulainen EJ, Johansson RT, Kellokoski JK, Nuutinen J, Kosma VM (2004) Versican expression in pharyngeal squamous cell carcinoma: an immunohistochemical study. J Clin Pathol 57(7):735–739PubMedPubMedCentralCrossRefGoogle Scholar
  97. Rahmani M, Wong BW, Ang L, Cheung CC, Carthy JM, Walinski H, McManus BM (2006) Versican: signaling to transcriptional control pathways. Can J Physiol Pharmacol 84(1):77–92PubMedCrossRefGoogle Scholar
  98. Ricciardelli C, Brooks JH, Suwiwat S, Sakko AJ, Mayne K, Raymond WA, Seshadri R, LeBaron RG, Horsfall DJ (2002) Regulation of stromal versican expression by breast cancer cells and importance to relapse-free survival in patients with node-negative primary breast cancer. Clin Cancer Res 8(4):1054–1060PubMedGoogle Scholar
  99. Ricciardelli C, Mayne K, Sykes PJ, Raymond WA, McCaul K, Marshall VR, Horsfall DJ (1998) Elevated levels of versican but not decorin predict disease progression in early-stage prostate cancer. Clin Cancer Res 4(4):963–971PubMedGoogle Scholar
  100. Ricciardelli C, Rodgers RJ (2006) Extracellular matrix of ovarian tumors. Semin Reprod Med 24(4):270–282PubMedCrossRefGoogle Scholar
  101. Ricciardelli C, Russell DL, Ween MP, Mayne K, Suwiwat S, Byers S, Marshall VR, Tilley WD, Horsfall DJ (2007) Formation of hyaluronan- and versican-rich pericellular matrix by prostate cancer cells promotes cell motility. J Biol Chem 282(14):10814–10825PubMedCrossRefGoogle Scholar
  102. Ricciardelli C, Sakko AJ, Ween MP, Russell DL, Horsfall DJ (2009) The biological role and regulation of versican levels in cancer. Cancer Metastasis Rev 28(1–2):233–245PubMedCrossRefGoogle Scholar
  103. Rivera CG, Bader JS, Popel AS (2011) Angiogenesis-associated crosstalk between collagens, CXC chemokines, and thrombospondin domain-containing proteins. Ann Biomed Eng 39(8):2213–2222PubMedPubMedCentralCrossRefGoogle Scholar
  104. Romeo S, Oosting J, Rozeman LB, Hameetman L, Taminiau AH, Cleton-Jansen AM, Bovee JV, Hogendoorn PC (2007) The role of noncartilage-specific molecules in differentiation of cartilaginous tumors: lessons from chondroblastoma and chondromyxoid fibroma. Cancer 110(2):385–394PubMedCrossRefGoogle Scholar
  105. Rooney P, Kumar S, Ponting J, Wang M (1995) The role of hyaluronan in tumor neovascularization (review). Int J Cancer 60:632–636PubMedCrossRefGoogle Scholar
  106. Rooney P, Wang M, Kumar P, Kumar S (1993) Angiogenic oligosaccharides of hyaluronan enhance the production of collagens by endothelial cells. J Cell Sci 105:213–218PubMedGoogle Scholar
  107. Russell DL, Ochsner SA, Hsieh M, Mulders S, Richards JS (2003) Hormone-regulated expression and localization of versican in the rodent ovary. Endocrinology 144(3):1020–1031PubMedCrossRefGoogle Scholar
  108. Said N, Sanchez-Carbayo M, Smith SC, Theodorescu D (2012) RhoGDI2 suppresses lung metastasis in mice by reducing tumor versican expression and macrophage infiltration. J Clin Invest 122(4):1503–1518PubMedPubMedCentralCrossRefGoogle Scholar
  109. Said N, Theodorescu D (2012) RhoGDI2 suppresses bladder cancer metastasis via reduction of inflammation in the tumor microenvironment. Oncoimmunology 1(7):1175–1177PubMedPubMedCentralCrossRefGoogle Scholar
  110. Sakko AJ, Ricciardelli C, Mayne K, Dours-Zimmermann MT, Zimmermann DR, Neufing P, Tilley WD, Marshall VR, Horsfall DJ (2007) Changes in steroid receptors and proteoglycan expression in the guinea pig prostate stroma during puberty and hormone manipulation. Prostate 67(3):288–300PubMedCrossRefGoogle Scholar
  111. Sakko AJ, Ricciardelli C, Mayne K, Suwiwat S, LeBaron RG, Marshall VR, Tilley WD, Horsfall DJ (2003) Modulation of prostate cancer cell attachment to matrix by versican. Cancer Res 63(16):4786–4791PubMedGoogle Scholar
  112. Sakko AJ, Ricciardelli C, Mayne K, Tilley WD, Lebaron RG, Horsfall DJ (2001) Versican accumulation in human prostatic fibroblast cultures is enhanced by prostate cancer cell-derived transforming growth factor beta1. Cancer Res 61(3):926–930PubMedGoogle Scholar
  113. Schönherr E, Järveläinen HT, Sandell LJ, Wight TN (1991) Effects of platelet-derived growth factor and transforming growth factor-β 1 on the synthesis of a large versican-like chondroitin sulfate proteoglycan by arterial smooth muscle cells. J Biol Chem 266:17640–17647PubMedGoogle Scholar
  114. Senda M, Fukuyama R, Nagasaka T (2016) Kinetics of versican-expressing macrophages in bone marrow after cord blood stem cell transplantation for treatment of acute myelogenous leukaemia. J Clin Pathol 69(10):906–911PubMedPubMedCentralCrossRefGoogle Scholar
  115. Shalapour S, Karin M (2015) Immunity, inflammation, and cancer: an eternal fight between good and evil. J Clin Invest 125(9):3347–3355PubMedPubMedCentralCrossRefGoogle Scholar
  116. Shen XH, Lin WR, MD X, Qi P, Dong L, Zhang QY, Ni SJ, Weng WW, Tan C, Huang D, Ma YQ, Zhang W, Sheng WQ, Wang YQ, Du X (2015) Prognostic significance of Versican expression in gastric adenocarcinoma. Oncogenesis 4:e178PubMedPubMedCentralCrossRefGoogle Scholar
  117. Skandalis SS, Kletsas D, Kyriakopoulou D, Stavropoulos M, Theocharis DA (2006a) The greatly increased amounts of accumulated versican and decorin with specific post-translational modifications may be closely associated with the malignant phenotype of pancreatic cancer. Biochim Biophys Acta 1760(8):1217–1225PubMedCrossRefGoogle Scholar
  118. Skandalis SS, Theocharis AD, Papageorgakopoulou N, Vynios DH, Theocharis DA (2006b) The increased accumulation of structurally modified versican and decorin is related with the progression of laryngeal cancer. Biochimie 88(9):1135–1143PubMedCrossRefGoogle Scholar
  119. Skandalis SS, Theocharis AD, Theocharis DA, Papadas T, Vynios DH, Papageorgakopoulou N (2004) Matrix proteoglycans are markedly affected in advanced laryngeal squamous cell carcinoma. Biochim Biophys Acta 1689(2):152–161PubMedCrossRefGoogle Scholar
  120. Slevin M, Krupinski J, Badimon L (2009) Controlling the angiogenic switch in developing atherosclerotic plaques: possible targets for therapeutic intervention. J Angiogenes Res 1:4PubMedPubMedCentralCrossRefGoogle Scholar
  121. Slevin M, Krupinski J, Gaffney J, Matou S, West D, Delisser H, Savani RC, Kumar S (2007) Hyaluronan-mediated angiogenesis in vascular disease: uncovering RHAMM and CD44 receptor signaling pathways. Matrix Biol 26(1):58–68PubMedCrossRefGoogle Scholar
  122. Sluiter NR, de Cuba EM, Kwakman R, Meijerink WJ, Delis-van Diemen PM, Coupe VM, Belien JA, Meijer GA, de Hingh IH, Te Velde EA (2016) Versican and vascular endothelial growth factor expression levels in peritoneal metastases from colorectal cancer are associated with survival after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Clin Exp Metastasis 33(4):297–307PubMedPubMedCentralCrossRefGoogle Scholar
  123. Sotoodehnejadnematalahi F, Staples KJ, Chrysanthou E, Pearson H, Ziegler-Heitbrock L, Burke B (2015) Mechanisms of hypoxic up-regulation of versican gene expression in macrophages. PLoS One 10(6):e0125799PubMedPubMedCentralCrossRefGoogle Scholar
  124. Stanton H, Melrose J, Little CB, Fosang AJ (2011) Proteoglycan degradation by the ADAMTS family of proteinases. Biochim Biophys Acta 1812(12):1616–1629PubMedCrossRefGoogle Scholar
  125. Steinman RM (2012) Decisions about dendritic cells: past, present, and future. Annu Rev Immunol 30:1–22PubMedCrossRefGoogle Scholar
  126. Suhovskih AV, Aidagulova SV, Kashuba VI, Grigorieva EV (2015) Proteoglycans as potential microenvironmental biomarkers for colon cancer. Cell Tissue Res 361(3):833–844PubMedCrossRefGoogle Scholar
  127. Suwiwat S, Ricciardelli C, Tammi R, Tammi M, Auvinen P, Kosma VM, LeBaron RG, Raymond WA, Tilley WD, Horsfall DJ (2004) Expression of extracellular matrix components versican, chondroitin sulfate, tenascin, and hyaluronan, and their association with disease outcome in node-negative breast cancer. Clin Cancer Res 10(7):2491–2498PubMedCrossRefGoogle Scholar
  128. Taipale J, Beachy PA (2001) The Hedgehog and Wnt signalling pathways in cancer. Nature 411(6835):349–354PubMedCrossRefGoogle Scholar
  129. Takahashi Y, Kuwabara H, Yoneda M, Isogai Z, Tanigawa N, Shibayama Y (2012) Versican G1 and G3 domains are upregulated and latent transforming growth factor-beta binding protein-4 is downregulated in breast cancer stroma. Breast Cancer 19(1):46–53PubMedCrossRefGoogle Scholar
  130. Tang M, Diao J, Gu H, Khatri I, Zhao J, Cattral MS (2015) Toll-like receptor 2 activation promotes tumor dendritic cell dysfunction by regulating IL-6 and IL-10 receptor signaling. Cell Rep 13(12):2851–2864PubMedCrossRefGoogle Scholar
  131. Theocharis AD, Skandalis SS, Tzanakakis GN, Karamanos NK (2010) Proteoglycans in health and disease: novel roles for proteoglycans in malignancy and their pharmacological targeting. FEBS J 277(19):3904–3923PubMedCrossRefGoogle Scholar
  132. Toole BP, Wight TN, Tammi MI (2002) Hyaluronan-cell interactions in cancer and vascular disease. J Biol Chem 277(7):4593–4596PubMedCrossRefGoogle Scholar
  133. Touab M, Arumi-Uria M, Barranco C, Bassols A (2003) Expression of the proteoglycans versican and mel-CSPG in dysplastic nevi. Am J Clin Pathol 119(4):587–593PubMedCrossRefGoogle Scholar
  134. Touab M, Villena J, Barranco C, Arumi-Uria M, Bassols A (2002) Versican is differentially expressed in human melanoma and may play a role in tumor development. Am J Pathol 160(2):549–557PubMedPubMedCentralCrossRefGoogle Scholar
  135. True LD, Hawley S, Norwood TH, Braun KR, Evanko SP, Chan CK, LeBaron RC, Wight TN (2009) The accumulation of versican in the nodules of benign prostatic hyperplasia. Prostate 69(2):149–158PubMedPubMedCentralCrossRefGoogle Scholar
  136. Tu K, Dou C, Zheng X, Li C, Yang W, Yao Y, Liu Q (2014) Fibulin-5 inhibits hepatocellular carcinoma cell migration and invasion by down-regulating matrix metalloproteinase-7 expression. BMC Cancer 14:938PubMedPubMedCentralCrossRefGoogle Scholar
  137. Udabage L, Brownlee GR, Waltham M, Blick T, Walker EC, Heldin P, Nilsson SK, Thompson EW, Brown TJ (2005) Antisense-mediated suppression of hyaluronan synthase 2 inhibits the tumorigenesis and progression of breast cancer. Cancer Res 65(14):6139–6150PubMedCrossRefGoogle Scholar
  138. Van Bockstal M, Lambein K, Van Gele M, De Vlieghere E, Limame R, Braems G, Van den Broecke R, Cocquyt V, Denys H, Bracke M, Libbrecht L, De Wever O (2014) Differential regulation of extracellular matrix protein expression in carcinoma-associated fibroblasts by TGF-beta1 regulates cancer cell spreading but not adhesion. Oncoscience 1(10):634–648PubMedPubMedCentralCrossRefGoogle Scholar
  139. Vizoso FJ, Gonzalez LO, Corte MD, Rodriguez JC, Vazquez J, Lamelas ML, Junquera S, Merino AM, Garcia-Muniz JL (2007) Study of matrix metalloproteinases and their inhibitors in breast cancer. Br J Cancer 96(6):903–911PubMedPubMedCentralCrossRefGoogle Scholar
  140. Voutilainen K, Anttila M, Sillanpaa S, Tammi R, Tammi M, Saarikoski S, Kosma VM (2003) Versican in epithelial ovarian cancer: relation to hyaluronan, clinicopathologic factors and prognosis. Int J Cancer 107(3):359–364PubMedCrossRefGoogle Scholar
  141. Wade A, Robinson AE, Engler JR, Petritsch C, James CD, Phillips JJ (2013) Proteoglycans and their roles in brain cancer. FEBS J 280(10):2399–2417PubMedPubMedCentralCrossRefGoogle Scholar
  142. Wang W, Xu GL, Jia WD, Ma JL, Li JS, Ge YS, Ren WH, Yu JH, Liu WB (2009) Ligation of TLR2 by versican: a link between inflammation and metastasis. Arch Med Res 40(4):321–323PubMedCrossRefGoogle Scholar
  143. Wang Z, Li Z, Wang Y, Cao D, Wang X, Jiang M, Li M, Yan X, Li Y, Liu Y, Luo F (2015) Versican silencing improves the antitumor efficacy of endostatin by alleviating its induced inflammatory and immunosuppressive changes in the tumor microenvironment. Oncol Rep 33(6):2981–2991PubMedGoogle Scholar
  144. Ween MP, Oehler MK, Ricciardelli C (2011) Role of versican, hyaluronan and CD44 in ovarian cancer metastasis. Int J Mol Sci 12(2):1009–1029PubMedPubMedCentralCrossRefGoogle Scholar
  145. West DC, Hampson IN, Arnold F, Kumar S (1985) Angiogenesis induced by degradation products of hyaluronic acid. Science 228:1324–1326PubMedCrossRefGoogle Scholar
  146. West DC, Kumar S (1989) The effect of hyaluronate and its oligosaccharides on endothelial cell proliferation and monolayer integrity. Exp Cell Res 183(1):179–196PubMedCrossRefGoogle Scholar
  147. Wight TN (2002) Versican: a versatile extracellular matrix proteoglycan in cell biology. Curr Opin Cell Biol 14(5):617–623PubMedCrossRefGoogle Scholar
  148. Wight TN, Kinsella MG, Evanko SP, Potter-Perigo S, Merrilees MJ (2014) Versican and the regulation of cell phenotype in disease. Biochim Biophys Acta 1840(8):2441–2451PubMedPubMedCentralCrossRefGoogle Scholar
  149. Wilkinson TS, Bressler SL, Evanko SP, Braun KR, Wight TN (2006) Overexpression of hyaluronan synthases alters vascular smooth muscle cell phenotype and promotes monocyte adhesion. J Cell Physiol 206(2):378–385PubMedCrossRefGoogle Scholar
  150. Woo M, Park K, Nam J, Kim JC (2007) Clinical implications of matrix metalloproteinase-1, -3, -7, -9, -12, and plasminogen activator inhibitor-1 gene polymorphisms in colorectal cancer. J Gastroenterol Hepatol 22(7):1064–1070PubMedCrossRefGoogle Scholar
  151. Wu Y, Chen L, Cao L, Sheng W, Yang BB (2004) Overexpression of the C-terminal PG-M/versican domain impairs growth of tumor cells by intervening in the interaction between epidermal growth factor receptor and β1-integrin. J Cell Sci 117(Pt 11):2227–2237PubMedCrossRefGoogle Scholar
  152. Wu YJ, La Pierre DP, Wu J, Yee AJ, Yang BB (2005) The interaction of versican with its binding partners. Cell Res 15(7):483–494PubMedCrossRefGoogle Scholar
  153. Xia L, Huang W, Tian D, Zhang L, Qi X, Chen Z, Shang X, Nie Y, Wu K (2014) Forkhead box Q1 promotes hepatocellular carcinoma metastasis by transactivating ZEB2 and VersicanV1 expression. Hepatology 59(3):958–973PubMedCrossRefGoogle Scholar
  154. Xiang YY, Dong H, Wan Y, Li J, Yee A, Yang BB, WY L (2006) Versican G3 domain regulates neurite growth and synaptic transmission of hippocampal neurons by activation of epidermal growth factor receptor. J Biol Chem 281(28):19358–19368PubMedCrossRefGoogle Scholar
  155. Yang BL, Zhang Y, Cao L, Yang BB (1999) Cell adhesion and proliferation mediated through the G1 domain of versican. J Cell Biochem 72(2):210–220PubMedCrossRefGoogle Scholar
  156. Yeung TL, Leung CS, Wong KK, Samimi G, Thompson MS, Liu J, Zaid TM, Ghosh S, Birrer MJ, Mok SC (2013) TGF-beta modulates ovarian cancer invasion by upregulating CAF-derived versican in the tumor microenvironment. Cancer Res 73(16):5016–5028PubMedPubMedCentralCrossRefGoogle Scholar
  157. Yoon H, Liyanarachchi S, Wright FA, Davuluri R, Lockman JC, de la Chapelle A, Pellegata NS (2002) Gene expression profiling of isogenic cells with different TP53 gene dosage reveals numerous genes that are affected by TP53 dosage and identifies CSPG2 as a direct target of p53. Proc Natl Acad Sci USA 99(24):15632–15637PubMedPubMedCentralCrossRefGoogle Scholar
  158. Zhang Y, Cao L, Kiani C, Yang BL, Hu W, Yang BB (1999) Promotion of chondrocyte proliferation by versican mediated by G1 domain and EGF-like motifs. J Cell Biochem 73(4):445–457PubMedCrossRefGoogle Scholar
  159. Zhang Y, Cao L, Yang BL, Yang BB (1998) The G3 domain of versican enhances cell proliferation via epidermal growth factor-like motifs. J Biol Chem 273(33):21342–21351PubMedCrossRefGoogle Scholar
  160. Zhang Z, Miao L, Wang L (2012) Inflammation amplification by versican: the first mediator. Int J Mol Sci 13(6):6873–6882PubMedPubMedCentralCrossRefGoogle Scholar
  161. Zheng PS, Vais D, Lapierre D, Liang YY, Lee V, Yang BL, Yang BB (2004a) PG-M/versican binds to P-selectin glycoprotein ligand-1 and mediates leukocyte aggregation. J Cell Sci 117(Pt 24):5887–5895PubMedCrossRefGoogle Scholar
  162. Zheng PS, Wen J, Ang LC, Sheng W, Viloria-Petit A, Wang Y, Wu Y, Kerbel RS, Yang BB (2004b) Versican/PG-M G3 domain promotes tumor growth and angiogenesis. FASEB J 18(6):754–756PubMedGoogle Scholar
  163. Zucker S, Vacirca J (2004) Role of matrix metalloproteinases (MMPs) in colorectal cancer. Cancer Metastasis Rev 23(1–2):101–117PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Paul A. Keire
    • 1
  • Inkyung Kang
    • 1
  • Thomas N. Wight
    • 1
    Email author
  1. 1.Matrix Biology ProgramBenaroya Research Institute at Virginia MasonSeattleUSA

Personalised recommendations