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

In metastatic processes, gene expression may variously alter through intera ctions between tumor and host stromal cells at the metastatic site. Using a tail vein injection-lung metastatic model and differential display, we ana lyzed alteration of gene expression in experimentally metastasized lesions. We found that expression of the c-met proto-oncogene was elevated in the l ungs metastasized by MC-1 cells. The up-regulation of c-met was also observ ed in the lungs metastasized by B16 melanoma cells. In situ hybridization a nalysis revealed that the elevation of c-met expression apparently occurred in tumor cells but did not in lung stromal cells at the metastatic site. T he c-Met protein was also highly expressed and phosphorylated. The up-regul ation of c-met appeared to be caused by induction of gene expression but no t to be due to preferential selection of tumor cells highly expressing c-me t. These findings suggest that the c-met proto-oncogene is up-regulated at the transcription level through some interactions between tumor and host st romal cells.