Background: Malignant transformation has been shown to be favored by the interaction between cancer cells and the tumor microenvironment, with a special role attributed to molecular components present in both compartments, such as proteoglycans, including Small Leucine-Rich Proteoglycans (SLRPs). SLRPs are increasingly recognized as powerful signaling molecules involved in cancer growth and inflammation. Recent studies suggest that, among other cancers, prostate cancer (PCa) undergoes changes in the expression patterns of these components of the extracellular matrix to promote their survival, growth, and spread. Growing evidence links inflammation to initiation and progression to advanced metastatic disease of PCa and other human cancers. Non-steroidal anti-inflammatory drugs (NSAIDs) have been associated with reduced risk of several cancers, including PCa. The protective effect of NSAIDs has been attributed to inhibition of cancer metastasis. The aim of this work was to determine the expression profiles of SLRPs in a highly metastatic prostate cancer cell line (PC-3) compared to a non-tumorigenic cell line (PWR-1E) and to identify the effects of NSAIDs in the expression patterns of these molecular components.

Methods: Differences in gene expression were determined by qRT-PCR for a panel of 15 SLRPs (ASPN, ECM2, LUM, PRELP, KERA, OMD, EPYC, OPTC, CHAD, NYX, PODN, OGN, BGN, FMOD, and DCN). Alterations in the expression of these genes in response to treatment with NSAIDs (ibuprofen and nimesulide) were also determined.

Results: Compared to non-tumorigenic PWR-1E cells, highly metastatic PC-3 cells showed higher expression levels of seven genes encoding SLRPs (FMOD, BGN, LUM, ASPN, ECM2, PRELP and EPYC). Of the remaining eight genes, DCN was not differentially expressed while PODN, NYX, KERA, OMD, OPTC, OGN and CHAD had not detectable expression in either PC-3 or PWR-1E cells. Treatment of PC-3 cells with ibuprofen and nimesulide affected the expression pattern of genes encoding SLRPs. Ibuprofen treatment increased the expression of PRELP and BGN and decreased the expression of EPYC and ECM2. On the other hand, nimesulide treatment resulted in increased expression of PRELP and decreased expression of LUM, EPYC and ECM2.

Conclusions: highly metastatic PC-3 cells had increased expression levels of SLRPs compared to non-tumorigenic PWR-1E cells. NSAIDs (Nimesulide and ibuprofen) changed the expression pattern of SLRPGs in metastatic PC-3 cells. Pharmacological effects of NSAIDs in prostate cancer warrants further investigation at the clinical settings. Additional studies are required to determine the clinical usefulness of NSAIDs in prostate cancer.

Citation Format: Niradiz Reyes, Juan Rebollo, Jan Geliebter. Effects of NSAIDs on gene expression of small leucine-rich proteoglycans in prostate cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 128.