Metastatic model for human prostate cancer using orthotopic implantation in nude mice

Background: Understanding the mechanism of prostate cancer metastasis is essential to the design of a more effective therapy. An effective therapy for this disease will depend on the development of a clinically relevant in vivo model. Purpose: We describe the development of such a model by using orthotopic implantation of human prostate cells in BALB/c nude mice. Method: We compared the tumori-genicity of and the incidence of metastasis of human prostate cancer PC-3M and LNCaP-FGC (LNCaP) cell lines subsequent to prostatic (orthotopic) or subcutaneous (ectopic) implantations in male nude mice. Results: LNCaP cells produced tumors only in the prostate. Enhanced tumorigenicity at the orthotopic site was found for PC-3M cells. Lymph node metastases were observed in practically all mice given an injection of PC-3M cells in the prostate, but they were uncommon with subcutaneous injection of these cells. Bilateral orchiectomy did not alter the tumorigenicity of either PC-3M or LNCaP cells or the incidence of lymph node metastasis by PC-3M cells. LNCaP tumors in the mouse prostate (but not PC-3M tumors) elaborated detectable levels of human prostate-specific antigen (PSA) in the serum, even when tumors were small (1.5 mm in diameter). Immuno- histochemistry analysis revealed the presence of the PSA marker in tissue sections of LNCaP but not of PC-3M tumors. Conclusions: The implantation of human prostate cancer cells in an ectopic environment does not permit expression of metastatic potential. In contrast, intraprostatic implantation does. Implications: These data suggest that the orthotopic injection of human prostate cancer cells into the nude mouse may provide a valuable model to study the biology and therapy of human prostate cancer.