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.
Thorax-Klinik der LVA Baden, Department of Medical Oncology, Heidelberg-Rohrbach, Germany.
J R
JR
Fischer
H
H
Darjes
H
H
Lahm
M
M
Schindel
P
P
Drings
P H
PH
Krammer
D018288:Carcinoma, Small Cell / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007376:Interleukin-2 / Q000037:antagonists & inhibitors; D008175:Lung Neoplasms / Q000378:metabolism*; D008938:Mitosis / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000378:metabolism* / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000378:metabolism
D007376:Interleukin-2; D016212:Transforming Growth Factor beta