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Gene Review

VCAN  -  versican

Homo sapiens

Synonyms: CSPG2, Chondroitin sulfate proteoglycan 2, Chondroitin sulfate proteoglycan core protein 2, ERVR, GHAP, ...
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Disease relevance of VCAN

  • RESULTS: Versican was strongly expressed in cellular crescents and periglomerular areas, whereas decorin and biglycan accumulated in collagen type I-enriched regions, including fibrocellular and fibrous crescents, and interstitial fibrosis [1].
  • Versican (chondroitin sulphate proteoglycan-2) is overexpressed in BPH and prostate cancer and potentially contributes to disease pathology [2].
  • We conclude that the deposition of versican is specific to the early remodelling process in both granulomatous and nongranulomatous lung diseases [3].
  • The results showed that in sarcoidosis, EAA and TB, the rim of connective tissue surrounding granulomas contained glycosaminoglycans and collagen, and that glycosaminoglycan staining corresponded to localization of versican [3].
  • Immunodetection of CS-6 and PG-M/version with the use of monoclonal antibodies 3-B-3 and 2-B-1 is therefore recommended as a useful tool in differentiating odontogenic myoma from myxoid MFH [4].
  • These results showing that AP-1 and TCF-4 binding sites are the main regulatory regions directing versican production provide new insights into versican promoter regulation during melanoma progression [5].

High impact information on VCAN


Chemical compound and disease context of VCAN

  • The 60-kDa glycoprotein appeared to be quite resistant to proteolysis, and comparison with GHAP from a viable glioma removed at surgery showed that the protein isolated from autopsy material was not a degradation product resulting from postmortem autolysis [9].
  • METHODS: One trochlea and its tendon from 11 dissecting-room cadavers were fixed in methanol, cryosectioned, and immunolabeled with a panel of monoclonal antibodies against types I, II, III, V, and VI collagens, chondroitin-4 and -6, keratan and dermatan sulfates, aggrecan, link protein, versican, and tenascin [10].
  • The association of hypermethylation of the clones obtained and transcriptional suppression in colorectal cancer was confirmed by examining the Versican gene, which we found to be silenced in methylated cell lines and reactivated by the methylation inhibitor 5-aza-2'-deoxycytidine [11].
  • Consistent with versican being the active inhibitory factor in the CM, the integrity of chondroitin sulfate side chains and an ability to bind the RGD (Arg-Gly-Asp) peptide sequence of fibronectin were essential for the inhibition of prostate cancer cell attachment to fibronectin [12].
  • We have identified a novel von Willebrand factor/fibrinogen/selectin-independent, platelet adhesion-promoting function of vascular PG-M/versicans that may be relevant in normal venous thrombosis and critical in atherosclerotic conditions [13].

Biological context of VCAN


Anatomical context of VCAN


Associations of VCAN with chemical compounds


Physical interactions of VCAN


Enzymatic interactions of VCAN

  • We conclude that versican V1 proteolysis in vivo can be catalyzed by one or more members of the ADAMTS family of metalloproteinases [30].

Co-localisations of VCAN


Regulatory relationships of VCAN

  • While vigorous trypsinization caused integrin cleavage and rendered the cells more susceptible to H(2)O(2)-induced damages, expression of versican or its C-terminal domain enhanced cell attachment and expression of beta1 integrin and fibronectin [31].
  • Therefore, we have asked if inhibiton of tyrosine kinase activity by genistein also blocks the stimulation of both versican core protein synthesis and glycosaminoglycan (GAG) chain modifications induced by PDGF in ASMCs [32].
  • Using stripe choice assays, we demonstrate that pure preparations of either a mixture of versican V0/V1 or V1 alone strongly inhibit the migration of multipotent Sox10/p75NTR double-positive early neural crest stem cells on fibronectin by interfering with cell-substrate adhesion [33].
  • Chondroitinase ABC treatment of the 900 kDa proteoglycan yielded a core protein with a molecular weight of approximately 400 kDa that was recognized by polyclonal antibodies against recombinantly expressed fusion proteins from human versican [34].
  • Exogenous addition of TGF-beta2 stimulated the versican transcript levels mainly by forcing osteosarcoma cells to express V1 and V0 isoforms [35].

Other interactions of VCAN

  • By using in vitro and in vivo assays, we showed CSPG2 to be directly transactivated by p53 [36].
  • Surprisingly, the length of HA required to accommodate two G1-domains was found to be significantly larger for aggrecan than versican, which may reflect differences in the conformation of HA stabilized on binding these proteins [37].
  • The connection between versican and fibrillin microfibrils may be functionally significant, particularly in cardiovascular tissues [16].
  • Both enzymes cleaved a recombinant versican substrate and native human versican at the Glu(441)-Ala(442) bond and the mature form of ADAMTS-4 was detected by Western analysis of extracts of aortic intima [30].
  • A sub-group of the ADAMTS lineage of metalloproteases possess versican-degrading properties and are potential regulators of proteoglycan accumulation associated with BPH [2].

Analytical, diagnostic and therapeutic context of VCAN


  1. Up-regulation of extracellular matrix proteoglycans and collagen type I in human crescentic glomerulonephritis. Stokes, M.B., Hudkins, K.L., Zaharia, V., Taneda, S., Alpers, C.E. Kidney Int. (2001) [Pubmed]
  2. The expression and regulation of ADAMTS-1, -4, -5, -9, and -15, and TIMP-3 by TGFbeta1 in prostate cells: relevance to the accumulation of versican. Cross, N.A., Chandrasekharan, S., Jokonya, N., Fowles, A., Hamdy, F.C., Buttle, D.J., Eaton, C.L. Prostate (2005) [Pubmed]
  3. Proteoglycans in granulomatous lung diseases. Bensadoun, E.S., Burke, A.K., Hogg, J.C., Roberts, C.R. Eur. Respir. J. (1997) [Pubmed]
  4. Immunohistochemical and histochemical characterization of the mucosubstances of odontogenic myxoma: histogenesis and differential diagnosis. Zhao, M., Lu, Y., Takata, T., Ogawa, I., Miyauchi, M., Mock, D., Nikai, H. Pathol. Res. Pract. (1999) [Pubmed]
  5. Structure and regulation of the versican promoter: the versican promoter is regulated by AP-1 and TCF transcription factors in invasive human melanoma cells. Domenzain-Reyna, C., Hernández, D., Miquel-Serra, L., Docampo, M.J., Badenas, C., Fabra, A., Bassols, A. J. Biol. Chem. (2009) [Pubmed]
  6. Versican: a versatile extracellular matrix proteoglycan in cell biology. Wight, T.N. Curr. Opin. Cell Biol. (2002) [Pubmed]
  7. Proteoglycan form of macrophage colony-stimulating factor binds low density lipoprotein. Suzu, S., Inaba, T., Yanai, N., Kawashima, T., Yamada, N., Oka, T., Machinami, R., Ohtsuki, T., Kimura, F., Kondo, S. J. Clin. Invest. (1994) [Pubmed]
  8. Versican is expressed in the proliferating zone in the epidermis and in association with the elastic network of the dermis. Zimmermann, D.R., Dours-Zimmermann, M.T., Schubert, M., Bruckner-Tuderman, L. J. Cell Biol. (1994) [Pubmed]
  9. Isolation and partial characterization of a glial hyaluronate-binding protein. Perides, G., Lane, W.S., Andrews, D., Dahl, D., Bignami, A. J. Biol. Chem. (1989) [Pubmed]
  10. Expression of a wide range of extracellular matrix molecules in the tendon and trochlea of the human superior oblique muscle. Milz, S., Regner, F., Putz, R., Benjamin, M. Invest. Ophthalmol. Vis. Sci. (2002) [Pubmed]
  11. Identification of differentially methylated sequences in colorectal cancer by methylated CpG island amplification. Toyota, M., Ho, C., Ahuja, N., Jair, K.W., Li, Q., Ohe-Toyota, M., Baylin, S.B., Issa, J.P. Cancer Res. (1999) [Pubmed]
  12. Modulation of prostate cancer cell attachment to matrix by versican. Sakko, A.J., Ricciardelli, C., Mayne, K., Suwiwat, S., LeBaron, R.G., Marshall, V.R., Tilley, W.D., Horsfall, D.J. Cancer Res. (2003) [Pubmed]
  13. Vascular PG-M/versican variants promote platelet adhesion at low shear rates and cooperate with collagens to induce aggregation. Mazzucato, M., Cozzi, M.R., Pradella, P., Perissinotto, D., Malmstrom, A., Morgelin, M., Spessotto, P., Colombatti, A., De Marco, L., Perris, R. FASEB J. (2002) [Pubmed]
  14. Accelerated age-related CpG island methylation in ulcerative colitis. Issa, J.P., Ahuja, N., Toyota, M., Bronner, M.P., Brentnall, T.A. Cancer Res. (2001) [Pubmed]
  15. Mapping of the versican proteoglycan gene (CSPG2) to the long arm of human chromosome 5 (5q12-5q14). Iozzo, R.V., Naso, M.F., Cannizzaro, L.A., Wasmuth, J.J., McPherson, J.D. Genomics (1992) [Pubmed]
  16. Versican interacts with fibrillin-1 and links extracellular microfibrils to other connective tissue networks. Isogai, Z., Aspberg, A., Keene, D.R., Ono, R.N., Reinhardt, D.P., Sakai, L.Y. J. Biol. Chem. (2002) [Pubmed]
  17. beta 1-Integrin-mediated glioma cell adhesion and free radical-induced apoptosis are regulated by binding to a C-terminal domain of PG-M/versican. Wu, Y., Chen, L., Zheng, P.S., Yang, B.B. J. Biol. Chem. (2002) [Pubmed]
  18. Characterization of the complete genomic structure of the human versican gene and functional analysis of its promoter. Naso, M.F., Zimmermann, D.R., Iozzo, R.V. J. Biol. Chem. (1994) [Pubmed]
  19. Differential regulation of extracellular matrix proteoglycan (PG) gene expression. Transforming growth factor-beta 1 up-regulates biglycan (PGI), and versican (large fibroblast PG) but down-regulates decorin (PGII) mRNA levels in human fibroblasts in culture. Kähäri, V.M., Larjava, H., Uitto, J. J. Biol. Chem. (1991) [Pubmed]
  20. Fibulin-1 is a ligand for the C-type lectin domains of aggrecan and versican. Aspberg, A., Adam, S., Kostka, G., Timpl, R., Heinegård, D. J. Biol. Chem. (1999) [Pubmed]
  21. The interaction of versican with its binding partners. Wu, Y.J., La Pierre, D.P., Wu, J., Yee, A.J., Yang, B.B. Cell Res. (2005) [Pubmed]
  22. Biglycan, decorin, and versican protein expression patterns in coronary arteriopathy of human cardiac allograft: distinctness as compared to native atherosclerosis. Lin, H., Wilson, J.E., Roberts, C.R., Horley, K.J., Winters, G.L., Costanzo, M.R., McManus, B.M. J. Heart Lung Transplant. (1996) [Pubmed]
  23. Expression of PG-M(V3), an alternatively spliced form of PG-M without a chondroitin sulfate attachment in region in mouse and human tissues. Zako, M., Shinomura, T., Ujita, M., Ito, K., Kimata, K. J. Biol. Chem. (1995) [Pubmed]
  24. Versican interacts with chemokines and modulates cellular responses. Hirose, J., Kawashima, H., Yoshie, O., Tashiro, K., Miyasaka, M. J. Biol. Chem. (2001) [Pubmed]
  25. Androgen receptor regulation of the versican gene through an androgen response element in the proximal promoter. Read, J.T., Rahmani, M., Boroomand, S., Allahverdian, S., McManus, B.M., Rennie, P.S. J. Biol. Chem. (2007) [Pubmed]
  26. The proteoglycans aggrecan and Versican form networks with fibulin-2 through their lectin domain binding. Olin, A.I., Mörgelin, M., Sasaki, T., Timpl, R., Heinegård, D., Aspberg, A. J. Biol. Chem. (2001) [Pubmed]
  27. Versican-thrombospondin-1 binding in vitro and colocalization in microfibrils induced by inflammation on vascular smooth muscle cells. Kuznetsova, S.A., Issa, P., Perruccio, E.M., Zeng, B., Sipes, J.M., Ward, Y., Seyfried, N.T., Fielder, H.L., Day, A.J., Wight, T.N., Roberts, D.D. J. Cell. Sci. (2006) [Pubmed]
  28. Lipoprotein lipase enhances the binding of native and oxidized low density lipoproteins to versican and biglycan synthesized by cultured arterial smooth muscle cells. Olin, K.L., Potter-Perigo, S., Barrett, P.H., Wight, T.N., Chait, A. J. Biol. Chem. (1999) [Pubmed]
  29. Calcium-dependent self-association of the C-type lectin domain of versican. Ney, A., Booms, P., Epple, G., Mörgelin, M., Guo, G., Kettelgerdes, G., Gessner, R., Robinson, P.N. Int. J. Biochem. Cell Biol. (2006) [Pubmed]
  30. Versican V1 proteolysis in human aorta in vivo occurs at the Glu441-Ala442 bond, a site that is cleaved by recombinant ADAMTS-1 and ADAMTS-4. Sandy, J.D., Westling, J., Kenagy, R.D., Iruela-Arispe, M.L., Verscharen, C., Rodriguez-Mazaneque, J.C., Zimmermann, D.R., Lemire, J.M., Fischer, J.W., Wight, T.N., Clowes, A.W. J. Biol. Chem. (2001) [Pubmed]
  31. Versican protects cells from oxidative stress-induced apoptosis. Wu, Y., Wu, J., Lee, D.Y., Yee, A., Cao, L., Zhang, Y., Kiani, C., Yang, B.B. Matrix Biol. (2005) [Pubmed]
  32. Genistein selectively inhibits platelet-derived growth factor-stimulated versican biosynthesis in monkey arterial smooth muscle cells. Schönherr, E., Kinsella, M.G., Wight, T.N. Arch. Biochem. Biophys. (1997) [Pubmed]
  33. Versican v0 and v1 guide migratory neural crest cells. Dutt, S., Kléber, M., Matasci, M., Sommer, L., Zimmermann, D.R. J. Biol. Chem. (2006) [Pubmed]
  34. Up-regulation of a chondroitin sulphate epitope during regeneration of mouse sciatic nerve: evidence that the immunoreactive molecules are related to the chondroitin sulphate proteoglycans decorin and versican. Braunewell, K.H., Martini, R., LeBaron, R., Kresse, H., Faissner, A., Schmitz, B., Schachner, M. Eur. J. Neurosci. (1995) [Pubmed]
  35. Transforming growth factor-beta as a key molecule triggering the expression of versican isoforms v0 and v1, hyaluronan synthase-2 and synthesis of hyaluronan in malignant osteosarcoma cells. Nikitovic, D., Zafiropoulos, A., Katonis, P., Tsatsakis, A., Theocharis, A.D., Karamanos, N.K., Tzanakakis, G.N. IUBMB Life (2006) [Pubmed]
  36. 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. Yoon, H., Liyanarachchi, S., Wright, F.A., Davuluri, R., Lockman, J.C., de la Chapelle, A., Pellegata, N.S. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  37. Expression and purification of functionally active hyaluronan-binding domains from human cartilage link protein, aggrecan and versican: formation of ternary complexes with defined hyaluronan oligosaccharides. Seyfried, N.T., McVey, G.F., Almond, A., Mahoney, D.J., Dudhia, J., Day, A.J. J. Biol. Chem. (2005) [Pubmed]
  38. Experimental immunity to the G1 domain of the proteoglycan versican induces spondylitis and sacroiliitis, of a kind seen in human spondylarthropathies. Shi, S., Ciurli, C., Cartman, A., Pidoux, I., Poole, A.R., Zhang, Y. Arthritis Rheum. (2003) [Pubmed]
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