Background: Thrombospondin (TSP), a cell matrix protein, and transforming growth factor ß (TGF-ß), a growth regulatory protein, play roles in tumor progression. The purpose of this study was to investigate the effects of TSP and TGF-ß on tumor cell invasion. Materials and methods: 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-ß and the cysteineserine-valine-threonine-cysteine-glycine (CSVTCG)-specific TSP receptor were also evaluated. Results: TSP caused a dose-dependent stimulation of tumor cell invasion. Antibodies against TSP, its CSVTCG-specific receptor, and TGF-ß inhibited TSP-promoted invasion by 50% to 71%. Conclusions: TSP and its CSVTCG-specific receptor promote KB cell invasion of collagen through the production and/or activation of TGF-ß. © 1995 Excerpta Medica, Inc. All rights reserved.