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(American Journal of Pathology. 2002;161:705-715.)
© 2002 American Society for Investigative Pathology

Animal Models

A Neuroendocrine/Small Cell Prostate Carcinoma Xenograft—LuCaP 49

Lawrence D. True*, Kent Buhler{dagger}, Janna Quinn{dagger}, Emily Williams{dagger}, Peter S. Nelson{ddagger}§, Nigel Clegg§, Jill A. Macoska, Thomas Norwood*, Alvin Liu{dagger}, William Ellis{dagger}, Paul Lange{dagger} and Robert Vessella{dagger}

From the Departments of Pathology,*Urology,{dagger}and Medicine,{ddagger}University of Washington, Seattle, Washington; the Section of Human Biology,§Fred Hutchinson Cancer Research Center, Seattle, Washington; and the Department of Urology,The University of Michigan School of Medicine, Ann Arbor, Michigan

Abstract

The late stages of progression of prostate carcinoma are typically characterized by an androgen-insensitive, rapidly proliferative state. Some late-stage tumors are composed predominantly of neuroendocrine cells. Virtually no animal models of a neuroendocrine/small cell variant of prostate carcinoma are available for experimental studies. We report a human neuroendocrine/small cell prostate carcinoma xenograft that was developed from a nodal metastasis of a human prostate carcinoma and that has been propagated as serial subcutaneous implants in severe combined immunodeficient mice for >4 years. Designated LuCaP 49, all tumor passages exhibit a neuroendocrine/small cell carcinoma phenotype—insensitivity to androgen deprivation, expression of neuroendocrine proteins, lack of expression of prostate-specific antigen or androgen receptor, and an unusually rapid growth (a doubling time of 6.5 days) for prostate cancer xenografts. Genetically this tumor exhibits loss of heterozygosity for the short arm of chromosome 8 and has a complex karyotype. This xenograft should prove to be useful in the investigation of mechanisms underlying the androgen-insensitive state of progressive prostate carcinoma.




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Copyright © 2002 by the American Society for Investigative Pathology.