title: Irradiation enhances the metastatic potential of prostatic small cell carcinoma xenografts.
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.
authors.affiliation: Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Lilach
authors.initials: L
authors.lastname: Agemy
authors.forename: Alon
authors.initials: A
authors.lastname: Harmelin
authors.forename: Tova
authors.initials: T
authors.lastname: Waks
authors.forename: Ilan
authors.initials: I
authors.lastname: Leibovitch
authors.forename: Tatyana
authors.initials: T
authors.lastname: Rabin
authors.forename: M Raphael
authors.initials: MR
authors.lastname: Pfeffer
authors.forename: Zelig
authors.initials: Z
authors.lastname: Eshhar
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000556:secondary; D000818:Animals; D018288:Carcinoma, Small Cell / Q000378:metabolism / Q000473:pathology* / Q000532:radiotherapy*; D049109:Cell Proliferation / Q000528:radiation effects*; D004195:Disease Models, Animal; D006801:Humans; D007680:Kidney Neoplasms / Q000556:secondary; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D009362:Neoplasm Metastasis / Q000532:radiotherapy; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000532:radiotherapy*; D023041:Xenograft Model Antitumor Assays
chemical_list: D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9