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Versican V1 isoform regulates cell‐associated matrix formation and cell behavior differentially from aggrecan in Swarm rat chondrosarcoma cells
Author(s) -
Wasa Junji,
Nishida Yoshihiro,
Shinomura Tamayuki,
Isogai Zenzo,
Futamura Naohisa,
Urakawa Hiroshi,
Arai Eisuke,
Kozawa Eiji,
Tsukushi Satoshi,
Ishiguro Naoki
Publication year - 2011
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.26230
Subject(s) - versican , aggrecan , extracellular matrix , proteoglycan , chondrosarcoma , transfection , chemistry , microbiology and biotechnology , chondroitin sulfate proteoglycan , cancer research , biology , pathology , medicine , biochemistry , osteoarthritis , gene , alternative medicine , articular cartilage
Versican, a large chondroitin sulfate proteoglycan that binds hyaluronan and is composed of large extracellular matrix aggregates, has been shown to correlate with tumor progression. No studies have examined the roles of versican in chondrosarcoma nor compared them to those of aggrecan. In clinical specimens of human chondromatous tumors, versican expression was significantly increased in malignant tumors, moreover, as the tumor grade increased. To clarify the roles of versican in chondrosarcoma, versican splicing variant 1, variant 3 or only GFP was stably transfected to Swarm rat chondrosarcoma cells with Trap‐In System. Forced expression of versican V1 isoform in Swarm rat chondrosarcoma cells induced a marked increase of cell‐associated matrix compared to V3‐, GFP‐ transfected or RCS cells. Versican was immunolocalized in a fashion similar to that of hyaluronan and more diffusively than aggrecan. Anchor‐dependent and ‐independent growth was not affected by versican isoform expression, whereas cell motility and migration were significantly enhanced by V1 isoform transfection. Tumors formed in vivo with V1‐transfected cells exhibited more myxomatous area and included more spindle shaped cells. These results support the concept that versican has the capacity to form more extensive cell‐associated matrix than aggrecan, and the prominent matrix formation alters the cell behavior of chondrosarcoma more aggressively. These observations suggest that versican expression may serve as a marker of tumor grade determination in chondrosarcoma and possibly help to decide on therapeutic targets in higher grades of chondrosarcoma.