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A Metastatic and Androgen-sensitive Human Prostate Cancer Model Using Intraprostatic Inoculation of LNCaP Cells in SCID Mice¹

Department of Cancer Endocrinology, British Columbia Cancer Agency, Vancouver, British Columbia, V5Z 4E6 Canada [N. S., M. E. G., N. B., P. S. R., E. B.], and Division of Urology, University of British Columbia, Vancouver, British Columbia, V5Z 355 Canada [M. E. G., L. D. S.]

Several metastasizing murine and human animal models for prostate cancer are available. However, these models are androgen-independent and lack differentiated features such as androgen receptor and androgen-regulated gene expression like prostate-specific antigen (PSA). The objective of this study was to develop a metastasizing prostate cancer model with differentiated features using the human LNCaP cell line. Athymic and SCID mice were injected either s.c. or intraprostatically with 1 x 10⁶ LNCaP cells. Changes in serum and tumor PSA mRNA levels were determined before and after castration to assess time to androgen-independent progression. Local tumor and metastatic growth was assessed at sacrifice after 12 weeks. Reverse transcription-PCR (RT-PCR) was used to detect circulating LNCaP cells. LNCaP tumor incidence after s.c. injection was 100% (65 of 65) in SCID mice and 80% in athymic mice. No lymph node or distant metastases were observed with s.c. tumors, and RT-PCR for PSA transcripts was negative. Primary tumor incidence after intraprostatic injection was 89% (39 of 44) in SCID mice and 60% in athymic mice. In 10 SCID mice with primary tumors followed for 12 weeks, retroperitoneal or mediastinal lymph node metastases were found in 100%, and microscopic pulmonary metastases were identified in 40%. RT-PCR for PSA transcripts was positive in 3 of 10 mice tested. Serum PSA levels in mice with s.c. and intraprostatic tumors decreased by 65% to nadir levels at 7 and 4 days after castration, respectively. Serum PSA and LNCaP tumor PSA mRNA levels increased to precastration levels earlier in SCID mice with intraprostatic tumors compared to those with s.c. tumors. Intraprostatic injection of LNCaP cells in SCID mice provides a useful animal model to investigate mechanisms of metastasis and to evaluate therapies targeted toward inhibiting the metastatic cascade.

¹ Supported in part by Grant 6-73535 from the National Cancer Institute of Canada and by the Lotte and John Hecht Memorial Foundation.

² To whom requests for reprints should be addressed, at Department of Cancer Endocrinology, British Columbia Cancer Agency, 600 West 10th Avenue, Vancouver, British Columbia, V5Z 4E6 Canada.

³ Current address: Institute of Experimental Medicine and Biotechnologies, Consiglio Nazionale delle Ricerche, Cosenza, Italy.

Received 6/26/96. Accepted 2/17/97.

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