A link between metastasis and resistance to apoptosis of variant small cell lung carcinoma.

A novel human gene CC3 with properties of a metastasis suppresor gene for small cell lung carcinoma (SCLC) is described. CC3 is an evolutionary conserved gene that is expressed ubiquitously in human tissues. CC3 RNA is absent in a subset of SCLC cell lines known as variant (v-SCLC) that are derived from tumors characterized by highly aggressive metastatic behavior. Introduction of CC3 into a variant SCLC line results in significant suppression of its metastasis in vivo. When deprived of growth factors in vitro, v-SCLC cells modified to express CC3 undergo rapid and massive cell death that at least partially could be ascribed to the activation of the apoptotic pathway. In addition, expression of CC3 in v-SCLC cells increases induction of apoptosis by chemoterapeutic drugs. Loss of CC3 in highly metastatic cells such as SCLC might render them resistant to death-inducing signals and thus help to ensure their survival under unfavorable conditions encountered in the metastatic process.