Transforming growth factor beta (
TGF-beta) promotes
tumor progression in some model systems including human
breast cancer cells. In this study, we report that human
breast cancer cell lines express reduced amounts of
TGF-beta type III receptor (RIII) when compared with untransformed human mammary epithelial cells. Consequently, we examined whether expression of RIII in human
breast cancer MDA-MB-231 cells could reduce
TGF-beta's
tumor promoting activity by sequestering active
TGF-beta isoforms produced by the cells. A
tetracycline-repressible human RIII expression vector was stably transfected into the cell line. RIII expression in a pool of transfected clones and a single clone was found to be reversibly repressed by
tetracycline treatment. Expression of RIII reduced the amount of active
TGF-beta1 and
TGF-beta2 in the
conditioned medium. The
medium conditioned by control cells showed a significantly higher growth inhibitory effect than that conditioned by RIII-transfected cells on the growth of the mink lung epithelial CCL64 cells. A
conditioned medium collected from RIII-transfected cells treated with
tetracycline significantly increased its growth inhibitory activity to that of control cells. Expression of RIII also reduced
tumor incidence and growth rate in two separate experiments when the cells were inoculated in athymic nude mice. Treatment of the mice with
tetracycline repressed RIII expression in the
tumors generated by RIII-transfected cells and increased
tumor incidence and growth rate. These results suggest that
TGF-beta RIII can reduce tumorigenicity of MDA-MB-231 cells apparently by sequestering
TGF-beta isoforms produced by these cells.