Phospholipase A2 activating protein induces tumor regression

There has been increasing interest in attempts to harness the body's normal inflammatory response mediated through the eicosanoid pathway to treat tumors. Accumulating data indicate that the growth of several different cancers is modulated by a group of pro-inflammatory bioactive lipids, the best known of which are the eicosanoids. Eicosanoid pathway constituents modulate cell function in several important ways, and an agent that activates PLA(2) and up-regulates LTB4 levels could be expected to be an effective cytotoxic tumor agent, especially if it stimulated NK cells. FLAP is a 28-kDa polypeptide that is a member of the WD-repeat protein, G-protein-transducin superfamily. The pro-inflammatory properties of FLAP have been elucidated using a number of different approaches. FLAP has been found in inflamed tissues and synovial fluid from patients with rheumatoid arthritis. Based on knowledge of FLAP as a pro-inflammatory agent, its capacity to modulate the immune response and the role of the inflammatory and immune responses in immune surveillance, the role of FLAP in cancer therapy was explored. Significant tumor regression was observed 72 hours following a single treatment with FLAP in an animal air pouch model of glioma, PEG-FLAP treatment increased the life expectancy of animals with Lewis lung cancer, and in preliminary studies in MTVL breast tumors in mice, FLAP treatment resulted in a similar increase in life expectancy. These findings suggest that FLAP holds promise as a potential therapy for cancer, and warrants further study. (C) 1998 Prous Science. All rights reserved.