Group III phospholipase A 2 promotes colitis and colorectal cancer

• Published in: Scientific reports Vol. 7; no. 1; p. 12261
• Main Authors: Murase, Remi, Taketomi, Yoshitaka, Miki, Yoshimi, Nishito, Yasumasa, Saito, Moe, Fukami, Kiyoko, Yamamoto, Kei, Murakami, Makoto
• Format: Journal Article
• Language: English
• Published: England 25-09-2017
• Subjects: Animals; Colitis - pathology; Colitis - physiopathology; Colon - pathology; Colorectal Neoplasms - pathology; Colorectal Neoplasms - physiopathology; Disease Susceptibility; Mice; Mice, Knockout; Phospholipases A2 - deficiency; Phospholipases A2 - metabolism
• ISSN: 2045-2322

Lipid mediators play pivotal roles in colorectal cancer and colitis, but only a limited member of the phospholipase A
(PLA
) subtypes, which lie upstream of various lipid mediators, have been implicated in the positive or negative regulation of these diseases. Clinical and biochemical evidence suggests that secreted PLA
group III (sPLA
-III) is associated with colorectal cancer, although its precise role remains obscure. Here we have found that sPLA
-III-null (Pla2g3
) mice are highly resistant to colon carcinogenesis. Furthermore, Pla2g3
mice are less susceptible to dextran sulfate-induced colitis, implying that the amelioration of colonic inflammation by sPLA
-III ablation may underlie the protective effect against colon cancer. Lipidomics analysis of the colon revealed significant reduction of pro-inflammatory/pro-tumorigenic lysophosholipids as well as unusual steady-state elevation of colon-protective fatty acids and their oxygenated metabolites in Pla2g3
mice. Overall, our results establish a role of sPLA
-III in the promotion of colorectal inflammation and cancer, expand our understanding of the divergent roles of multiple PLA
enzymes in the gastrointestinal tract, and point to sPLA
-III as a novel druggable target for colorectal diseases.