Marshall Urist Award. Interstitial collagenase gene expression correlates with in vitro invasion in human...

Matrix metalloproteinases contribute to the processes of local invasion and metastasis by providing cells with the ability to traverse tissue boundaries. The levels of gene expression were quantitated for matrix metalloproteinases-1 and tissue inhibitors of metalloproteinases-1 in human chondrosarcoma cell lines, and the results were correlated with cell differentiation, collagenase activity, and in vitro invasion. Three well characterized human cell lines were used in this study, with the level of chondrocytic differentiation confirmed to be JJ012, FS090, and 105KC in increasing order on the basis of aggrecan and collagen gene expression. The matrix metalloproteinases-1/tissue inhibitors of metalloproteinases-1 ratio correlated with the level of differentiation in an inverse fashion. Collagenase activity paralleled matrix metalloproteinases-1/tissue inhibitors of metalloproteinases-1 gene expression and was associated with a more invasive phenotype in an in vitro assay. In this report, matrix metalloproteinase-1 and tissue inhibitors of metalloproteinases-1 expression in human chondrosarcoma tumor cell lines were quantitated, and it was shown that interstitial collagenase gene expression correlates inversely with chondrocytic differentiation. Differences in collagenase activity and in vitro invasion correlate inversely with the level of differentiation. These findings are consistent with the hypothesis that collagenase activity is associated with a poorer prognosis in chondrosarcoma by facilitating cell egress from the tumor matrix.