The GPR 55 agonist, L-α-lysophosphatidylinositol, mediates ovarian carcinoma cell-induced angiogenesis.

摘要: Background and Purpose Highly vascularized ovarian carcinoma secretes the putative endocannabinoid GPR55 agonist, L-α-lysophosphatidylinositol (LPI), into circulation. We aimed to assess involvement of this agonist its receptor in cancer angiogenesis. Experimental Approach Secretion LPI by three cell lines (OVCAR-3, OVCAR-5 COV-362) was tested mass spectrometry. Involvement cell-derived on angiogenesis vivo chicken chorioallantoic membrane (CAM) assay along with assessment effect proliferation, network formation, migration neonatal adult human endothelial colony-forming cells (ECFCs). Engagement verified using pharmacological inhibitor CID16020046 diminution expression four different target-specific siRNAs. To study underlying signal transduction, Western blot analysis performed. Key Results Ovarian stimulated CAM assay. Applied ECFCs in vitro vivo CAM. The inhibited LPI-stimulated ECFC formation as well cell- LPI-induced vivo. Four siRNAs against prevented these effects angiogenesis. These pro-angiogenic were transduced GPR55-dependent phosphorylation ERK1/2 p38 kinase. Conclusions Implications We conclude that inhibiting LPI/GPR55 pathway appears a promising target carcinoma.