{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T03:58:10Z","timestamp":1778731090912,"version":"3.51.4"},"reference-count":33,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2008,2,4]],"date-time":"2008-02-04T00:00:00Z","timestamp":1202083200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Prostate"],"published-print":{"date-parts":[[2008,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>Small cell carcinoma of the prostate (SCCP) is a rare subset of prostate cancer (0.5\u20132% 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>Using SCID mice, the response to fractionated ionizing radiation (IR) of two unique human NE xenografts of SCCP (WISH\u2010PC2 and WM\u20104A) was investigated.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Fractionated irradiation of WISH\u2010PC2 xenografts using total doses of &gt;24 Gy induced a delay in tumor growth, while total doses of &gt;36 Gy led to local tumor eradication. However, most of the irradiated mice suffered from disseminated metastases. Similarly, in the WM\u20104A xenograft, a total dose of 20 Gy led to tumor growth delay and some of the mice also developed metastases. Non\u2010irradiated 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\u2010scapular regions, areas rich in brown adipose tissue. A correlation was found between the appearance of irradiation\u2010induced metastases and activation of the gelatinase activity of matrix metalloproteinase\u20109.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>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. Prostate 68: 530\u2013539, 2008. \u00a9 2008 Wiley\u2010Liss, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pros.20702","type":"journal-article","created":{"date-parts":[[2008,2,4]],"date-time":"2008-02-04T18:32:22Z","timestamp":1202149942000},"page":"530-539","source":"Crossref","is-referenced-by-count":13,"title":["Irradiation enhances the metastatic potential of prostatic small cell carcinoma xenografts"],"prefix":"10.1002","volume":"68","author":[{"given":"Lilach","family":"Agemy","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alon","family":"Harmelin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tova","family":"Waks","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilan","family":"Leibovitch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatyana","family":"Rabin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. 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