Selective Stimulation of Small Cell Lung Cancer Clonal Growth by Bombesin and Gastrin-releasing Peptide1

Human small cell lung cancers (SCLC) produce and secrete the regulatory peptide bombesin (BN) or its mammalian counterpart gastrinreleasing peptide (GRP). In addition, several SCLC tumor lines have been shown to express high affinity receptors for BN/GRP. On the basis of these findings, we investigated the effect of exogenously added BN and GRP on the soft agarose colony growth of a panel of human cell lines. In serum-free defined medium, colony formation of 9 of 10 SCLC cell lines was stimulated up to ISO-fold by BN or GRP, with peak colony stimulation observed at SO nM BN. In contrast, no stimulatory effect of BN was observed on nine non-SCLC cell lines. Although no stimulation of colony growth by BN was seen in serum-supplemented medium, addition of BN to the serum-free medium increased cloning efficiency to that achieved by serum in most of the SCLC cell lines. GRP 1-27, the active mammalian analogue of Bn, stimulated colony growth of SCLC cells similar to the manner of BN, while the physiologically inactive BN analogue, des-Leu (13)-Met (I4)-B\. had no effect on colony growth. No correlation was observed in SCLC cell lines between the response of these cells to exogenous BN and the amount of cellular BN/GRP pro duced or the presence of BN receptors. These data suggest that BN/GRP may in some instances function as an autocrine growth factor for SCLC and indicate new ways for modulating SCLC growth in patients with this tumor.