This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kim, J. Articles by Menter, D. G. Search for Related Content PubMed PubMed Citation Articles by Kim, J. Articles by Menter, D. G.

Suppression of Prostate Tumor Cell Growth by Stromal Cell Prostaglandin D Synthase–Derived Products

Departments of ¹ Genitourinary Medical Oncology, ² Experimental Therapeutics, and ³ Clinical Cancer Prevention, The University of Texas M.D. Anderson Cancer Center, Houston, Texas

Requests for reprints: David G. Menter, Department of Clinical Cancer Prevention, The University of Texas M.D. Anderson Cancer Center, Box 1360, 1515 Holcombe Boulevard, Houston, TX 77030. Phone: 713-792-0626; Fax: 713-794-4403; E-mail: dmenter{at}mdanderson.org.

Stromal-epithelial interactions and the bioactive molecules produced by these interactions maintain tissue homeostasis and influence carcinogenesis. Bioactive prostaglandins produced by prostaglandin synthases and secreted by the prostate into seminal plasma are thought to support reproduction, but their endogenous effects on cancer formation remain unresolved. No studies to date have examined prostaglandin enzyme production or prostaglandin metabolism in normal prostate stromal cells. Our results show that lipocalin-type prostaglandin D synthase (L-PGDS) and prostaglandin D₂ (PGD₂) metabolites produced by normal prostate stromal cells inhibited tumor cell growth through a peroxisome proliferator–activated receptor (PPAR)–dependent mechanism. Enzymatic products of stromal cell L-PGDS included high levels of PGD₂ and 15-deoxy-^12,14-PGD₂ but low levels of 15-deoxy-^12,14-prostaglandin J₂. These PGD₂ metabolites activated the PPAR ligand-binding domain and the peroxisome proliferator response element reporter systems. Thus, growth suppression of PPAR-expressing tumor cells by PGD₂ metabolites in the prostate microenvironment is likely to be an endogenous mechanism involved in tumor suppression that potentially contributes to the indolence and long latency period of this disease.

This article has been cited by other articles:

				C. A. Payne, S. Maleki, M. Messina, M. G. O'Sullivan, G. Stone, N. R. Hall, J. F. Parkinson, H. R. Wheeler, R. J. Cook, M. T. Biggs, et al. Loss of prostaglandin D2 synthase: a key molecular event in the transition of a low-grade astrocytoma to an anaplastic astrocytoma Mol. Cancer Ther., October 1, 2008; 7(10): 3420 - 3428. [Abstract] [Full Text] [PDF]

				J. M. Park, Y. Kanaoka, N. Eguchi, K. Aritake, S. Grujic, A. M. Materi, V. S. Buslon, B. L. Tippin, A. M. Kwong, E. Salido, et al. Hematopoietic Prostaglandin D Synthase Suppresses Intestinal Adenomas in ApcMin/+ Mice Cancer Res., February 1, 2007; 67(3): 881 - 889. [Abstract] [Full Text] [PDF]

				C. W. Tam, A. S. Cheng, R. Y. M. Ma, K.-M. Yao, and S. Y. W. Shiu Inhibition of Prostate Cancer Cell Growth by Human Secreted PDZ Domain-Containing Protein 2, a Potential Autocrine Prostate Tumor Suppressor Endocrinology, November 1, 2006; 147(11): 5023 - 5033. [Abstract] [Full Text] [PDF]

				D. M. Ray, F. Akbiyik, and R. P. Phipps The Peroxisome Proliferator-Activated Receptor {gamma} (PPAR{gamma}) Ligands 15-Deoxy-{Delta}12,14-Prostaglandin J2 and Ciglitazone Induce Human B Lymphocyte and B Cell Lymphoma Apoptosis by PPAR{gamma}-Independent Mechanisms J. Immunol., October 15, 2006; 177(8): 5068 - 5076. [Abstract] [Full Text] [PDF]

				S. E. Feldon, C. W. O'Loughlin, D. M. Ray, S. Landskroner-Eiger, K. E. Seweryniak, and R. P. Phipps Activated Human T Lymphocytes Express Cyclooxygenase-2 and Produce Proadipogenic Prostaglandins that Drive Human Orbital Fibroblast Differentiation to Adipocytes Am. J. Pathol., October 1, 2006; 169(4): 1183 - 1193. [Abstract] [Full Text] [PDF]

				M. A. Peraza, A. D. Burdick, H. E. Marin, F. J. Gonzalez, and J. M. Peters The Toxicology of Ligands for Peroxisome Proliferator-Activated Receptors (PPAR) Toxicol. Sci., April 1, 2006; 90(2): 269 - 295. [Abstract] [Full Text] [PDF]

				K-M Fung, E N S Samara, C Wong, A Metwalli, R Krlin, B Bane, C Z Liu, J T Yang, J V Pitha, D J Culkin, et al. Increased expression of type 2 3{alpha}-hydroxysteroid dehydrogenase/type 5 17{beta}-hydroxysteroid dehydrogenase (AKR1C3) and its relationship with androgen receptor in prostate carcinoma. Endocr. Relat. Cancer, March 1, 2006; 13(1): 169 - 180. [Abstract] [Full Text] [PDF]