Induction of c-met proto-oncogene expression at the metastatic site.

In metastatic processes, gene expression may variously alter through interactions between tumor and host stromal cells at the metastatic site. Using a tail vein injection-lung metastatic model and differential display, we analyzed alteration of gene expression in experimentally metastasized lesions. We found that expression of the c-met proto-oncogene was elevated in the lungs metastasized by MC-1 cells. The up-regulation of c-met was also observed in the lungs metastasized by B16 melanoma cells. In situ hybridization analysis revealed that the elevation of c-met expression apparently occurred in tumor cells but did not in lung stromal cells at the metastatic site. The c-Met protein was also highly expressed and phosphorylated. The upregulation of c-met appeared to be caused by induction of gene expression but not to be due to preferential selection of tumor cells highly expressing c-met. These findings suggest that the c-met proto-oncogene is up-regulated at the transcription level through some interactions between tumor and host stromal cells.