A soluble transforming growth factor beta type III receptor suppresses tumorigenicity and metastasis of human breast cancer MDA-MB-231 cells

Transforming growth factor beta (TGF-beta) can promote late stage tumor pro gression in a number of model systems. In the present study, we have examin ed whether expression of a truncated soluble extracellular domain of TGF-be ta type LU receptor (sRIII) in human breast cancer MDA-MB-231 cells can ant agonize the tumor-promoting activity of TGF-beta by sequestering active TGF -beta isoforms that are produced by the cancer cells. The secretion of sRII I reduced the amount of active TGF-beta, and TGF-beta, in the conditioned m edium. This led to a significant reduction of the growth-inhibitory activit y of the medium conditioned by sRIII-expressing cells on the growth of mink lung epithelial CCL64 cells in comparison with the medium conditioned by t he control cells. The tumor incidence and growth rate of all of the three s RIII-expressing clones studied were significantly lower than those of the c ontrol cells in athymic nude mice. Four of five control cell-inoculated mic e showed spontaneous metastasis in the lung, whereas none of the sam-expres sing cell-inoculated mice had any lung metastasis, Thus, our results sugges t that the sRIII may be used to antagonize the tumor-promoting activity of TGF-beta.