Mechanisms of metastatic spread of high aggressive tumors such as small cell lung cancer (SCLC) are poorly understood. A unique SCID-hu metastasis model was developed that for the first time allows metastasis of SCLC to be studied in the experimental in vivo setting. Molecular analysis of SCLC cell lines with different metastatic potentials have led to the identification of a novel human gene designated CC3 whose expression is lacking in metastatic cells. Introduction of CC3 into SCLC cells suppresses their ability to form metastatic tumors in the SCID-hu mice. The goal of this project then is to prove that CC3 is a metastasis suppressor gene in small cell lung cancer and to analyze the mechanisms of metastasis suppression by CC3. The functional relevance of the lack of expression of CC3 to the metastatic phenotype of SCLC will be further confirmed in the in vivo metastasis assays. The clinical relevance and potential prognostic significance of CC3 expression will be evaluated through analysis of its expression in clinical tumor specimens. The mechanism of metastasis-suppression by CC3 will be addressed in experiments designed to define the effects of CC3 expression on the phenotype of metastatic cells. These investigators anticipate that the results of these studies will advance the understanding of the mechanisms of metastasis of SCLC. Lack of CC3 protein could have prognostic significance in patients diagnosed with SCLC and potentially other tumors. A thorough understanding of CC3 function might eventually lead to the development of new anti-metastatic therapies.