The roles of sPLA2-IIA (Pla2g2a) in cancer of the small and large intestine

The mouse secretory phospholipase A2 group IIA (sPLA₂-IIA) gene Pla2g2a has been identified as a susceptibility gene for cancer of the small and large intestine. Interestingly, unlike most previously identified tumor susceptibility genes, Pla2g2a does not behave like a classical oncogene or tumor suppressor gene. Hence, identification of its biological functions in tumor development may shed new light on general mechanisms that modulate colon cancer risk. So far, sPLA₂-IIA has been proposed to play a role in anti-bacterial defense, inflammation and eicosanoid generation, in clearance of apoptotic cells, and in the Wnt signaling pathway. More recently, comparison of RNA expression profiles of colon from Pla2g2a-transgenic to Pla2g2a-deficient mice confirmed and even extended sPLA₂-IIA's diverse biological effects. In this review we aim to summarize current knowledge about the various links of SPLA₂-IIA to cancer of the gastro-intestinal tract, and propose several models to illustrate its putative biological effects on tumor development.