Expression of hyaluronan synthase 2 or hyaluronidase 1 differentially affect the growth rate of transplantable colon carcinoma cell tumors.
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.
Jacobson
Annica
A
Department of Medical Biochemistry and Microbiology, Biomedical Center, Uppsala University, SE-751 23 Uppsala, Sweden.
Rahmanian
Mehdi
M
Rubin
Kristofer
K
Heldin
Paraskevi
P
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
D018076:DNA, Complementary; D006820:Hyaluronic Acid; D014453:Glucuronosyltransferase; C491097:Has2 protein, rat; D000076002:Hyaluronan Synthases; D006821:Hyaluronoglucosaminidase