Orthotopic model of renal cell carcinoma

A human renal cancer was first established in continuous culture in 1962. Currently, there are well over 100 different characterized renal cancer cell lines derived from both primary and metastatic renal cell carcinomas (RCCs) (1-3). The biological phenotype of cultured renal cancer cells typically includes a sustained and essentially unlimited growth capacity, a lack of contact inhibition and anchorage dependence, a capacity to form tumors in athymic mice, and an aneuploid karyotype including nonrandom chromosomal abnormalities (1,2). The antigenic phenotype of RCCs as determined by monoclonal antibodies (mAbs) generated against cell-surface glycoproteins, glycolipids, and blood-group antigens of renal cancers provide a series of phenotypic markers which characterize these tumors (4-6). Many of these mAbs also react with the proximal tubule portion of the human nephron, confirming earlier studies indicating that >90% of renal cancers derive from epithelial cells of the proximal tubule (7,8). While established RCC cell lines have frequently been analyzed for molecular defects, their greatest utility has been to screen combinations of chemotherapeutic and biologic agents for antiproliferative activity (9-12). Short-term cultures of renal cancer cells derived from fresh tumor specimens have similarly been used to screen drugs (13), but inhibitory effects in vitro have not been shown to predict a response in vivo (i.e., in human patients).