EVIDENCE FOR A POSITIVE ROLE OF TRANSFORMING GROWTH-FACTOR-BETA IN HUMAN BREAST-CANCER CELL TUMORIGENESIS

To determine the biological role of transforming growth factor-beta (T GF-beta) in mammary carcinomas in vivo, estrogen-dependent MCF-7 cells were transfected with a mouse TGF-beta1 cDNA. Growth characteristics in culture were not altered in the transfected cells. However, the MCF -7/TGF-beta1 cells formed tumors in ovariectomized athymic mice in the absence of estrogen supplementation. Daily injections of human recomb inant TGF-beta1 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-beta antibodies on tumor formation by estrogen-independent MDA-231 cells was examined. The 2G7 IgG2b (2G7) antibody, which neutralizes TGF-beta1, -beta2, an d -beta3, blocked the formation of MDA-231 tumors at the injection sit e and lung metastases in nude mice. Inoculation of MDA-231 cells inhib ited, while injection of 2G7 increased mouse spleen natural killer (NK ) activity. 2G7 did not inhibit MDA-231 tumors and metastases in NK-de ficient animals. Finally, medium conditioned by MDA-231 cells inhibite d lymphocyte-mediated NK activity; this inhibition was abrogated by 2G 7, but not by a control IgG2. These data support a positive role for t umor cell TGF-beta in the maintenance and/or progression of mammary ca rcinoma cells in an intact host. (C) 1993 Wiley-Liss, Inc.