OVEREXPRESSION OF NORMAL C-SRC IN POORLY METASTATIC HUMAN COLON-CANCER CELLS ENHANCES PRIMARY TUMOR-GROWTH BUT NOT METASTATIC POTENTIAL

Whereas genetic paradigms are now defined for the development of human colon cancer, little is known regarding the mechanisms that regulate development of the metastatic phenotype. Recent reports have indirectl y linked the expression and activation of c-Src to the process of huma n colon cancer metastasis. Whereas v-Src, a highly activated mutationa l derivative of c-Src, has been shown to induce metastasis, normal c-S rc has not been tested for this property. We hypothesized that c-Src o verexpression in the milieu of a poorly metastatic cancer cell might p ermit the development of a highly metastatic cell. Two poorly metastat ic human colon cancer cell lines were stably transfected with expressi on vectors encoding normal human c-Src. Clones producing 4-10-fold mor e c-Src than controls were injected s.c. and intrasplenically into the nude mouse to assess primary tumor growth and liver metastatic potent ial. Whereas metastatic potential was unaffected, primary tumor growth in vivo was significantly enhanced by c-Src overexpression. No effect s on rates of tumor cell proliferation were seen in vitro. Our finding s suggest that normal c-Src may be necessary but is insufficient for t he induction of the metastatic phenotype.