Among all the existing isoforms, secretory PLA2 is the major target for inhibitor development, since many studies have proven that this enzyme participates in various inflammatory conditions, such as cancer, Alzheimer and arthritis.
Several recent studies revealed that phospholipid metabolising enzyme, phospholipase A2 (PLA<sub>2</sub>), is a critical regulator of cancer accelerating pathologies and apoptosis in several types of cancers.
Specifically, we found that survival of cancer cells was critically dependent on phospholipase A2 (PLA2) to mobilize lysophospholipids and free fatty acids to sustain fatty acid oxidation and oxidative phosphorylation.
Overexpression of secretory phospholipase A2-IIa supports cancer stem cell phenotype via HER/ERBB-elicited signaling in lung and prostate cancer cells.
Loss of secreted phospholipase A2 receptor (PLA2R1) has recently been found to render human primary cells more resistant to senescence whereas increased PLA2R1 expression is able to induce cell cycle arrest, cancer cell death or blockage of cancer cell transformation in vitro, suggesting that PLA2R1 displays tumor suppressive activities.
Several studies indicate that phospholipase A(2) (PLA(2)) expression and/or activation account for the high levels of arachidonic acid (AA) detected in cancer and, together with the elevated expression of cyclooxygenase-2, lead to cell proliferation and tumor formation.
To investigate the role of group II phospholipase A2(PLA2) in cancer, we examined the expression and secretion of group II PLA2 in response to the stimulation of interleukin 6(IL-6) in human gastric cancer cells in vitro.