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Xenograft Models of Human Prostate Cancer

  • Chapter
Prostate Cancer

Part of the book series: Contemporary Cancer Research ((CCR))

Abstract

Prostate cancer (CaP) is the second-leading cause of cancer deaths among men in the Western world. Understanding the biology of CaP is essential to the development of novel therapeutic strategies. To do this effectively, researchers need access to cell lines, animal models, and biospecimens. Ideally, these should reflect characteristics of the disease from early diagnosis through the period of androgen-independent metastases. However, the biology of CaP is extraordinarily complex. The primary tumors are heterogeneous and multifocal. They almost uniformly produce a number of biomarkers, such as prostate-specific antigen, prostate acid phosphatase, human kallikrein 2, prostate-specific membrane antigen, and prostate stem cell antigen. The tumors are characteristically androgen dependent, and respond favorably to androgen ablation for a variable period, after which time, they progress to an androgen refractory state, wherein the low androgen levels are no longer growth inhibitory. Progression also involves metastases, primarily to the lymph nodes and bone. Unlike other epithelial tumors that metastasize to bone, CaP results in a notoriously osteoblastic response characterized by the formation of new bone. Thus, CaP presents to the investigator a very dynamic, biologically diverse set of characteristics during its course from early disease to bone metastases. Unfortunately, no single model mimics all of the features of human CaP, but by using a combination of models, nearly all of the biological characteristics can be studied to some degree.

In this chapter, we review the various xenograft models of human CaP that are available for study. We look at the method of generating xenografts, including the host strains and sites of implantation. We report on the models that are best suited for the study of progression from androgen dependence to androgen independence. Unfortunately, spontaneous metastases to bone resulting in an osteoblastic response are an extremely rare event in these models, but several methods that attempt to circumvent this limitation are reviewed. Overall, several examples that demonstrate the wealth of new knowledge being provided by use of these preclinical human CaP xenograft models are provided throughout the chapter.

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Authors and Affiliations

  1. Department of Urology, University of Washington Medical Center, Seattle, WA

    Eva Corey PhD

  2. Puget Sound VA Health Care System and Department of Urology, University of Washington Medical Center, Seattle, WA

    Robert L. Vessella PhD

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  1. Eva Corey PhD
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  2. Robert L. Vessella PhD
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Editors and Affiliations

  1. Emory University School of Medicine, Atlanta, GA

    Leland W. K. Chung PhD

  2. Johns Hopkins University School of Medicine, Baltimore, MD

    William B. Isaacs PhD

  3. Prostate Cancer Foundation, Santa Monica, CA

    Jonathan W. Simons MD

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© 2007 Humana Press Inc., Totowa, NJ

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Corey, E., Vessella, R.L. (2007). Xenograft Models of Human Prostate Cancer. In: Chung, L.W.K., Isaacs, W.B., Simons, J.W. (eds) Prostate Cancer. Contemporary Cancer Research. Humana Press. https://doi.org/10.1007/978-1-59745-224-3_1

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  • DOI: https://doi.org/10.1007/978-1-59745-224-3_1

  • Publisher Name: Humana Press

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