The biologicbehavior of tumorcells is partially controlled by the microenvironment. We investigated the expression levels of several genes involved in metastasis and drug response in RENCA cells growing in ectopic (skin) and orthotopic (kidney) sites. MATERIALS AND
RENCA cells growing in the kidney of syngeneic mice produced metastatic lesions in the lung (57% of mice), while the same cells growing in the subcutis did not. Tumors growing in the kidney were more resistant to DXR than tumors growing in the subcutis. MTT assays revealed that tumorcells derived from kidney were more resistant to DXR than those cells from subcutis. In situ hybridization analyses showed that transcripts of EGFR and type IV collagenasegenes in kidneytumors were higher than those of subcutaneous tumors but mdr expression showed no difference between the two tumors.