ISOLATION AND CHARACTERIZATION OF METASTATIC VARIANTS FROM HUMAN TRANSITIONAL-CELL CARCINOMA PASSAGED BY ORTHOTOPIC IMPLANTATION IN ATHYMICNUDE-MICE

Purpose: These studies were designed to develop an orthotopic model fo r human bladder cancer and to isolate variant metastatic cell lines. M aterials and Methods: The human bladder cancer cell line 253J was impl anted into the muscular wall of the bladder of athymic nude mice. By i n vivo recycling, we selected for 2 variant cell lines: 253J B-V, a bl adder Line isolated after 5 serial passages in the bladder, and 253J l ung-IV, established from a lung tumor nodule that was recycled through the bladder. Results: These 2 cell Lines showed enhanced tumorigenici ty, as measured by a decreased latent period, and rapid growth as comp ared with the parental cell line. Moreover, orthotopic implantation of these cell lines resulted in metastasis to the lungs. These in vivo-s elected, metastatic cell lines exhibited unique karyotypic alterations , increased anchorage-independent growth, overexpression of basic fibr oblast growth factor, altered expression of adhesion molecules and the ability to migrate through Matrigel. Conclusions: This reproducible m odel of human bladder cancer offers the opportunity to study cellular properties associated with tumor progression and metastasis and is sui table for the evaluation of new therapeutic strategies for invasive bl adder cancer.