Abstract

Thrombospondin (TSP), a cell matrix protein, and transforming growth factor beta (TGF-beta), a growth regulatory protein, play roles in tumor progression. The purpose of this study was to investigate the effects of TSP and TGF-beta on tumor cell invasion. Tumor cell invasion assays were performed using a modified Boyden chamber apparatus with collagen-coated membranes. The KB oral carcinoma cell line was studied in serum-free media. Invasion was measured as the summation of the number of cells in five representative low-power fields (x 100) traversing the collagen barrier after a 3-hour incubation period. The effects of antibodies against TSP, TGF-beta and the cysteine-serine-valine-threonine-cysteine-glycine (CSVTCG)-specific TSP receptor were also evaluated. TSP caused a dose-dependent stimulation of tumor cell invasion. Antibodies against TSP, its CSVTCG-specific receptor, and TGF-beta inhibited TSP-promoted invasion by 50% to 71%. TSP and its CSVTCG-specific receptor promote KB cell invasion of collagen through the production and/or activation of TGF-beta.

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