Canna~Fangled Abstracts

The G-protein coupled receptor 55-agonist L-α-lysophosphatidylinositol mediates ovarian carcinoma cell induced angiogenesis.

By May 18, 2015No Comments
2015 May 18. doi: 10.1111/bph.13196. [Epub ahead of print]

Abstract

PM 1aBACKGROUND AND PURPOSE:

Highly vascularized ovarian carcinoma secretes the putative endocannabinoid and G-protein coupled receptor 55 (GPR55) ligand L-α-lysophosphatidylinositol (LPI) into the circulation. We aimed to elucidate the involvement of LPI/GPR55 in ovarian cancer angiogenesis.

EXPERIMENTAL APPROACH:

Secretion of LPI by three ovary cancer cell lines (OVCAR-3, OVCAR-5 and COV-362) was tested by mass spectrometery. Involvement of cancer cell-derived LPI on angiogenesis was tested in the in vivo chicken chorioallantoic membrane (CAM) assay along with the assessment of the effect of LPI on proliferation, network-formation, migration of neonatal and adult human endothelial colony-forming cells (ECFCs). Engagement of GPR55 was verified by using its pharmacological inhibitor CID16020046 and diminution of GPR55 expression by four respective target-specific siRNAs. To study underlying signal transduction Western blot analysis were performed.

KEY RESULTS:

Ovarian carcinoma cell-derived LPI stimulated angiogenesis in the CAM assay. Applied LPI stimulated proliferation, network-formation, migration of neonatal and ECFCs in vitro and angiogenesis in the in vivo CAM. The pharmacological GPR55-inhibitor CID16020046 inhibited LPI-stimulated ECFC proliferation, network-formation and migration in vitro as well as ovarian carcinoma cells- and LPI-induced angiogenesis in vivo. Four target-specific siRNAs against GPR55 prevented the effect of LPI on angiogenesis. These pro-angiogenic effects of LPI where induced by GPR55-dependent phosphorylation of ERK1/2 and p38 kinase.

CONCLUSIONS AND IMPLICATIONS:

We conclude that inhibiting the pro-angiogenic LPI/GPR55-pathway appears a promising target against angiogenesis in ovarian carcinoma.
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PMID:

 

25989290

 

[PubMed – as supplied by publisher]
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