Characterization of a Human, Sex Steroid-responsive Transitional Cell Carcinoma Maintained as a Tumor Line (R198) in Athymic Nude Mice1

We have established a transplantable tumor line, R198, de rived from a papillary (transitional cell) carcinoma of the human urinary bladder. In nude mice, the tumor line exhibits properties attributable to both prostatic and transitional epithelia. In tumorbearing animals given androgens, the neoplasm has a rapid growth rate, possesses low levels of measurable androgen receptors, produces tartrate-inhibitable acid phosphatase, and forms well-encapsulated, cystic tumors composed of transitional, glandular, and squamous cells. The administration of estrogens or transplantation of the tumor into female mice causes regres sion of the tumor. In a small percentage of the transplants placed into females or estrogenized animals, selection occurs for tumor cells which can grow under these conditions. The resulting tumors are infiltrating scirrhous carcinomas that closely resemble squamous cell carcinomas of the urinary bladder. These neo plasms grow slowly and do not possess androgen receptors or secretory material. They are composed of a homogeneous pop ulation of squamous cells which are locally invasive. The paradox of a bladder tumor with some prostatic charac teristics may be explained by the fact that the tumor was derived from the trigone region of the bladder, which embryologically is formed by an admixture of tissue from the wolfñanduct and the urogenital sinus. Some trigone-derived neoplasms have charac teristics of both bladder and prostate. We hypothesize that sex steroid-sensitive R198, with characteristics of both bladder tran sitional cells and prostatic epithelia, is a tumor which phenotypically expresses the embryological origins of these tissues. As such, the tumor line will serve as a useful model for studying sex steroid-responsive cells of the urogenital epithelium.