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Bladder Cancer Xenografts: A Model of Tumor Cell Heterogeneity¹

Urological Cancer Research Unit Laboratories, Department of Surgery [P.J.R., D.R., J.P., M.J.] and Ludwig Institute for Cancer Research [P.G.], University of Sydney, Sydney, New South Wales, 2006; Kanematsu Laboratories [J.W., R.A.Z., P.C.V.] and Department of Anatomical Pathology [J.P., E.J.W.], Royal Prince Alfred Hospital, Sydney, New South Wales, 2050, Australia

Twenty bladder biopsies from patients with primary transitional cell carcinoma were inoculated into nude mice. To date, eleven of these have grown as primary implants and three serially transplantable xenograft lines (UCRU-BL-12, UCRU-BL-13, UCRU-BL-14) have been established. The histological and ultrastructural features of human transitional cell carcinoma have been maintained in each line. Despite a relatively uniform histological appearance, several indices of occult tumor heterogeneity have been revealed. Immunocytochemical staining was negative for ß-subunit human chorionic gonadotrophin but positive for carcinoembryonic antigen only in areas of squamous differentiation. All three tumors bound peanut lectin. Flow cytometric DNA analysis of UCRU-BL-13 showed multiple aneuploid peaks, separate populations being demonstrated in different xenografts of the same generation. However, the morphologies of these tumors remained identical. On initial implantation UCRU-BL-12 and UCRU-BL-14 were near diploid but aneuploid populations became apparent with increasing passage number. Each xenograft line caused cachexia in the host mice. Treatment with the cisplatin analogue, isopropyl platinum, ameliorated the cachexia displayed by mice carrying UCRU-BL-14 but did not cause tumor regression. UCRU-BL-12, when tested with cisplatin, isopropyl platinum, and carboplatin, showed equivalent growth retardation with each drug. These xenografted human bladder cancers may be useful models for the study of heterogeneity of the tumor populations in bladder cancer and for the evaluation of new approaches to treatment.

¹ Supported by a grant from the National Health and Medical Research Council of Australia.

² To whom requests for reprints should be addressed, at Urological Cancer Research Unit, Royal Prince Alfred Hospital, Missenden Road, Camperdown, New South Wales 2050, Australia.

Received 8/ 9/85. Revised 12/16/85. Accepted 12/20/85.

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