Evidence for a positive role of transforming growth factor‐β in human breast cancer cell tumorigenesis

To determine the biological role of transforming growth factor‐β (TGF‐β) in mammary carcinomas in vivo, estrogen‐dependent MCF‐7 cells were transfected with a mouse TGF‐β1 cDNA. Growth characteristics in culture were not altered in the transfected cells. However, the MCF‐7/TGF‐β1 cells formed tumors in ovariectomized athymic mice in the absence of estrogen supplementation. Daily injections of human recombinant TGF‐β1 supported tumor formation by wild‐type MCF‐7 cells in castrated nude mice in the absence of exogenous estradiol. In another approach to the same question, the effect of anti‐TGF‐β antibodies on tumor formation by estrogen‐independent MDA‐231 cells was examined. The 2G7 IgG2b (2G7) antibody, which neutralizes TGF‐β1, −β2, and −β3, blocked the formation of MDA‐231 tumors at the injection site and lung metastases in nude mice. Inoculation of MDA‐231 cells inhibited, while injection of 2G7 increased mouse spleen natural killer (NK) activity. 2G7 did not inhibit MDA‐231 tumors and metastases in NK‐deficient animals. Finally, medium conditioned by MDA‐231 cells inhibited lymphocyte‐mediated NK activity; this inhibition was abrogated by 2G7, but not by a control IgG2. These data support a positive role for tumor cell TGF‐β in the maintenance and/or progression of mammary carcinoma cells in an intact host.