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 lu ng cancer (SCLC) cell lines on modulation of cytokine-induced growth o f lymphocytes, We found that interleukin-2 (IL-2)-mediated T-cell grow th was inhibited by a cytokine constitutively secreted by the SCLC cel l line, NCI-N417. Of several cytokines tested, only transforming growt h factor beta(1) (TGF beta(1)) severely suppressed IL-2-dependent T-ce ll growth. Using a specific anti-TGF beta(1) antibody, we found that t his antibody blocked the immunosuppressive activity secreted by NCI-N4 17. Thus, the NCI-N417-derived immunosuppressive molecule was serologi cally identified as TGF beta(1). Further experiments showed that TGF b eta(1) was secreted by four of eight SCLC lines tested. mRNA for TGF b eta(1) was expressed in NCI-N417 and in SCLC-22H. Constitutive secreti on of biologically active TGF beta(1) by SCLC lines suggests that tumo ur-derived immunosuppression may have clinical relevance.