Isolation and Characterization of Metastatic Variants from Human Transitional Cell Carcinoma Passaged by Orthotopic Implantation in Athymic Nude Mice

Abstract

These studies were designed to develop an orthotopic model for human bladder cancer and to isolate variant metastatic cell lines. The human bladder cancer cell line 253J was implanted into the muscular wall of the bladder of athymic nude mice. By in vivo recycling, we selected for 2 variant cell lines: 253J B-V, a bladder line isolated after 5 serial passages in the bladder, and 253J lung-IV, established from a lung tumor nodule that was recycled through the bladder. These 2 cell lines showed enhanced tumorigenicity, as measured by a decreased latent period, and rapid growth as compared with the parental cell line. Moreover, orthotopic implantation of these cell lines resulted in metastasis to the lungs. These in vivo-selected, metastatic cell lines exhibited unique karyotypic alterations, increased anchorage-independent growth, overexpression of basic fibroblast growth factor, altered expression of adhesion molecules and the ability to migrate through Matrigel. This reproducible model of human bladder cancer offers the opportunity to study cellular properties associated with tumor progression and metastasis and is suitable for the evaluation of new therapeutic strategies for invasive bladder cancer.