CONSTITUTIVE SECRETION OF BIOACTIVE TRANSFORMING GROWTH-FACTOR BETA(1) BY SMALL-CELL LUNG-CANCER CELL-LINES

We investigated effects of soluble mediators secreted by small cell lung cancer (SCLC) cell lines on modulation of cytokine-induced growth of lymphocytes, We found that interleukin-2 (IL-2)-mediated T-cell growth was inhibited by a cytokine constitutively secreted by the SCLC cell line, NCI-N417. Of several cytokines tested, only transforming growth factor beta(1) (TGF beta(1)) severely suppressed IL-2-dependent T-cell growth. Using a specific anti-TGF beta(1) antibody, we found that this antibody blocked the immunosuppressive activity secreted by NCI-N417. Thus, the NCI-N417-derived immunosuppressive molecule was serologically identified as TGF beta(1). Further experiments showed that TGF beta(1) was secreted by four of eight SCLC lines tested. mRNA for TGF beta(1) was expressed in NCI-N417 and in SCLC-22H. Constitutive secretion of biologically active TGF beta(1) by SCLC lines suggests that tumour-derived immunosuppression may have clinical relevance.