title: Expression of hyaluronan synthase 2 or hyaluronidase 1 differentially affect the growth rate of transplantable colon carcinoma cell tumors.
abstract: Advanced colorectal cancers are often associated with elevated amounts of hyaluronan. To investigate the importance of hyaluronan in colon carcinoma tumor progression, we have expressed by stable transfection hyaluronan synthase 2 (Has2) and hyaluronidase 1 (Hyal1) in the rat colon carcinoma cell line, PROb. We found that hyaluronan overproduction led to a higher growth rate of tumor cells in vitro, and to a faster development of transplantable tumors in syngeneic rats, compared to the mock-transfectants. Has2 transfected PROb cells gave rise to tumors that were significantly less vascularized, but had a significantly larger viable tumor fraction compared to tumors generated from mock-transfectants. In contrast, Hyal1 overexpression suppressed the growth rate of tumor cells both in vitro and in vivo. Moreover, tumors derived from Hyal1-transfected cells had a significantly larger necrotic area than tumors derived from mock- and Has2-transfectants. Our study demonstrates that Has2 overproduction promotes tumorigenicity, whereas Hyal1 overexpression suppresses tumorigenicity in an experimental model for colon carcinoma.
authors.affiliation: Department of Medical Biochemistry and Microbiology, Biomedical Center, Uppsala University, SE-751 23 Uppsala, Sweden.
authors.forename: Annica
authors.initials: A
authors.lastname: Jacobson
authors.forename: Mehdi
authors.initials: M
authors.lastname: Rahmanian
authors.forename: Kristofer
authors.initials: K
authors.lastname: Rubin
authors.forename: Paraskevi
authors.initials: P
authors.lastname: Heldin
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D002455:Cell Division; D003110:Colonic Neoplasms / Q000378:metabolism*; D018076:DNA, Complementary / Q000378:metabolism; D005260:Female; D014453:Glucuronosyltransferase / Q000096:biosynthesis* / Q000378:metabolism; D000076002:Hyaluronan Synthases; D006820:Hyaluronic Acid / Q000378:metabolism; D006821:Hyaluronoglucosaminidase / Q000096:biosynthesis*; D007150:Immunohistochemistry; D008297:Male; D011485:Protein Binding; D051381:Rats; D013997:Time Factors; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D018076:DNA, Complementary; D006820:Hyaluronic Acid; D014453:Glucuronosyltransferase; C491097:Has2 protein, rat; D000076002:Hyaluronan Synthases; D006821:Hyaluronoglucosaminidase