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  • Title: Irradiation enhances the metastatic potential of prostatic small cell carcinoma xenografts.
    Author: Agemy L, Harmelin A, Waks T, Leibovitch I, Rabin T, Pfeffer MR, Eshhar Z.
    Journal: Prostate; 2008 Apr 01; 68(5):530-9. PubMed ID: 18247403.
    Abstract:
    BACKGROUND: Small cell carcinoma of the prostate (SCCP) is a rare subset of prostate cancer (0.5-2% of all prostatic carcinomas), predominantly composed of neuroendocrine (NE) cells, with a very poor prognosis. Irradiation is one of the mainstay options for SCCP local treatment, yet, little is known about the clinical response of these aggressive tumors to radiotherapy. METHODS: Using SCID mice, the response to fractionated ionizing radiation (IR) of two unique human NE xenografts of SCCP (WISH-PC2 and WM-4A) was investigated. RESULTS: Fractionated irradiation of WISH-PC2 xenografts using total doses of >24 Gy induced a delay in tumor growth, while total doses of >36 Gy led to local tumor eradication. However, most of the irradiated mice suffered from disseminated metastases. Similarly, in the WM-4A xenograft, a total dose of 20 Gy led to tumor growth delay and some of the mice also developed metastases. Non-irradiated local xenografts failed to disseminate, even following surgical excision of the main tumor mass; however, tumor cells administered intravenously did form metastases. Metastases of both xenografts were located in the adrenal/kidney and inter-scapular regions, areas rich in brown adipose tissue. A correlation was found between the appearance of irradiation-induced metastases and activation of the gelatinase activity of matrix metalloproteinase-9. CONCLUSIONS: Clinically, this study raises the possibility that radiation to SCCP may promote metastatic disease. For patients in whom prostate biopsy shows a predominance of small cell cancer, it may be necessary to deliver systemic therapy together with the radiotherapy in order to prevent the development of metastases.
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