Gene expression Profiles of Lysophosphatidic Acid-Related Molecules in the Prostate: Relevance to Prostate Cancer and Benign Hyperplasia

OBJECTIVE. To elucidate gene expression profiles of lysophosphatidic acid (LPA)-related molecules in cancer, pre-cancerous lesion, and benign hyperplasia of the prostate. MATERIALS AND METHODS. Prostate tissue samples were surgically obtained from 10 patients with localized prostate cancer and seven patients with invasive bladder cancer. Cancer cells and the corresponding stromal cells from normal prostate, high grade intraepithelial neoplasia (HGPIN), benign hyperplastic glands were isolated by laser capture microdissection. mRNA levels of three LPA receptors, LPA1, LPA2, LPA3, two LPA-synthesizing enzymes, autotaxin (ATX), acylglycerol kinase (AGK), and a LPA-degradation enzyme, prostatic acid phosphatase (PAP), were quantitatively assessed. The expression levels of the same genes were also determined in three human prostate cancer cell lines LNCaP, PC-3, and DU-145. RESULTS. LPA1 mRNA level was significantly decreased in HGPIN and cancer epithelia when compared to the benign glands. LPA3 mRNA level was elevated in cancer epithelia compared to benign glands. LPA3, AGK, and PAP were predominantly expressed in LNCaP cells while LPA1 and ATX gene expressions were found in PC-3 and Du-145 cells. In BPH, AGK was abundantly expressed in the stroma while PAP was predominant in epithelial cells. CONCLUSIONS. By acting via LPA3, LPA may play an important role in the development of prostate cancer. Switching of LPA receptor expression from LPA3 to LPA1, may be involved in prostate cancer progression and/or androgen independence. LPA may also play a key role in the development of benign prostatic hyperplasia. Prostate 69:283-292,2009. (C) 2008 Wiley-Liss. Inc.