Expression of secretory phospholipase A2 in colon tumor cells potentiates tumor growth

✍ Scribed by Glenn S. Belinsky; Thiruchandurai V. Rajan; Elizabeth A. Saria; Charles Giardina; Daniel W. Rosenberg

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: English
• Weight: 620 KB
• Volume: 46
• Category: Article
• ISSN: 0899-1987
• DOI: 10.1002/mc.20271

✦ Synopsis

Abstract

Secretory phospholipase A~2~ (sPLA~2~‐IIA) has been shown to attenuate intestinal tumorigenesis in Apc^Min^ mice, demonstrating that it is a tumor modifier. To further explore the actions of sPLA~2~‐IIA in tumorigenesis, sPLA~2~‐IIA was overexpressed in two cell lines where it is normally absent, the murine colon tumor cell line AJ02nm~0~, and human colon carcinoma cell line HCT‐116. Two allelic variants of sPLA~2~‐IIA were tested in this study; sPLA~2~‐IIA^AKR^ and sPLA~2~‐IIA^SWR^, which are derived from AKR/J and SWR/J mice, respectively, and differ by a single amino acid at position 63 in the calcium‐ and receptor‐binding domain. There was no change in cell‐doubling time for either allele when compared to vector controls. Furthermore, sodium butyrate and arachidonic acid (AA)‐induced cell death were unchanged in control and transfected cells. Addition of the sPLA~2~ substrate, palmitoyl‐arachidonoyl‐phosphatidic acid (PAPA), to AJ02nm~0~ cells resulted in a modest (12%–24%), but significant (P < 0.01), inhibition of growth that was dependent on sPLA~2~‐IIA expression. However, when AJ02nm~0~ and HCT‐116 cells were injected subcutaneously (sc) into nude mice, Pla2g2a expression resulted in a 2.5‐fold increase in tumor size. In addition, sPLA~2~‐IIA expressing HCT‐116 tumors were found to be more infiltrative than controls. We conclude that the ability of sPLA~2~‐IIA to slow tumor cell growth is dependent upon the availability of substrate, and that in some instances sPLA~2~‐IIA may actually enhance tumor growth. Mechanisms that may account for differences between the tumor explant model versus the Apc^Min^ model of intestinal cancer are discussed. © 2006 Wiley‐Liss, Inc.