In this study we used the subrenal capsule site of C57BL/6J mice to assess the tumorigenic and metastatic potential of established urothelial cell lines in a syngeneic murine model. High tumor take and subsequent removal of the primary tumor by nephrectomy resulted in the extended lifespan of the animals enabling the formation of secondary tumor growth. To test this model we have used a panel of cell lines expressing constitutively, or following transfection, ras oncogene products. All cell lines constitutively expressing ras oncogenes (K, H, or N-ras) were tumorigenic and metastatic in this assay. One non tumorigenic cell line (BBN3) and one tumorigenic but non-metastatic cell line (SH264), remained non-metastatic following transfection with the pSV2-neo gene but formed micrometastases in the lung when a ras oncogene was introduced in the same manner. Expression of altered ras proteins following transfection in these two cell lines was demonstrated using an H-ras specific antibody in Western blot analysis. This study demonstrates the value of the subrenal capsule site as a metastatic assay for bladder cancer and the potential involvement of ras oncogenes in urothelial cell metastasis.
Animals Carcinoma, Renal Cell