Potential role of group X secretory phospholipase A2 in cyclooxygenase-2-dependent PGE2 formation during colon tumorigenesis

AbstractAlthough the cyclooxygenase-2 (COX-2) pathway of the arachidonic acid cascade has been suggested to play an important role in colon carcinogenesis, there is little information concerning the identity of phospholipase A2 (PLA2) involved in the arachidonic acid release in colon tumors. Here, we compared the potencies of three types of secretory PLA2s (group IB, IIA and X sPLA2s) for the arachidonic acid release from cultured human colon adenocarcinoma cells, and found that group X sPLA2 has the most powerful potency in the release of arachidonic acid leading to COX-2-dependent prostaglandin E2 (PGE2) formation. Furthermore, immunohistological analysis revealed the elevated expression of group X sPLA2 in human colon adenocarcinoma neoplastic cells in concert with augmented expression of COX-2. These findings suggest a critical role of group X sPLA2 in the PGE2 biosynthesis during colon tumorigenesis

Hair Follicular Expression and Function of Group X Secreted Phospholipase A2 in Mouse Skin*

Although perturbed lipid metabolism can often lead to skin abnormality, the role of phospholipase A2 (PLA2) in skin homeostasis is poorly understood. In the present study we found that group X-secreted PLA2 (sPLA2-X) was expressed in the outermost epithelium of hair follicles in synchrony with the anagen phase of hair cycling. Transgenic mice overexpressing sPLA2-X (PLA2G10-Tg) displayed alopecia, which was accompanied by hair follicle distortion with reduced expression of genes related to hair development, during a postnatal hair cycle. Additionally, the epidermis and sebaceous glands of PLA2G10-Tg skin were hyperplasic. Proteolytic activation of sPLA2-X in PLA2G10-Tg skin was accompanied by preferential hydrolysis of phosphatidylethanolamine species with polyunsaturated fatty acids as well as elevated production of some if not all eicosanoids. Importantly, the skin of Pla2g10-deficient mice had abnormal hair follicles with noticeable reduction in a subset of hair genes, a hypoplasic outer root sheath, a reduced number of melanin granules, and unexpected up-regulation of prostanoid synthesis. Collectively, our study highlights the spatiotemporal expression of sPLA2-X in hair follicles, the presence of skin-specific machinery leading to sPLA2-X activation, a functional link of sPLA2-X with hair follicle homeostasis, and compartmentalization of the prostanoid pathway in hair follicles and epidermis