Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

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"Köpfe" der aktuellen Meldungen:

Nina Höller

Nariae Baik-Schneditz

Bernhard Schwaberger

Lukas Peter Mileder

Niels Hammer

Gerhard Pichler

Roland Malli

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SHR Neuro Krebs Kardio Lipid Stoffw Microb

Hofmann, NA; Yang, J; Trauger, SA; Nakayama, H; Huang, L; Strunk, D; Moses, MA; Klagsbrun, M; Bischoff, J; Graier, WF.
The GPR 55 agonist, L-α-lysophosphatidylinositol, mediates ovarian carcinoma cell-induced angiogenesis.
Br J Pharmacol. 2015; 172(16):4107-4118 Doi: 10.1111/bph.13196 [OPEN ACCESS]
Web of Science PubMed FullText FullText_MUG

Führende Autor*innen der Med Uni Graz: Graier Wolfgang; Hofmann Nicole
Co-Autor*innen der Med Uni Graz: Strunk Dirk
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Abstract:: Highly vascularized ovarian carcinoma secretes the putative endocannabinoid and GPR55 agonist, L-α-lysophosphatidylinositol (LPI), into the circulation. We aimed to assess the involvement of this agonist and its receptor in ovarian cancer angiogenesis. Secretion of LPI by three ovarian cancer cell lines (OVCAR-3, OVCAR-5 and COV-362) was tested by mass spectrometry. 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, and 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 different target-specific siRNAs. To study underlying signal transduction, Western blot analysis was performed. Ovarian carcinoma cell-derived LPI stimulated angiogenesis in the CAM assay. Applied LPI stimulated proliferation, network formation, and migration of neonatal 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 cell- and LPI-induced angiogenesis in vivo. Four target-specific siRNAs against GPR55 prevented these effects of LPI on angiogenesis. These pro-angiogenic effects of LPI were transduced by GPR55-dependent phosphorylation of ERK1/2 and p38 kinase. We conclude that inhibiting the pro-angiogenic LPI/GPR55 pathway appears a promising target against angiogenesis in ovarian carcinoma. © 2015 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of The British Pharmacological Society.
Find related publications in this database (using NLM MeSH Indexing): Animals -; Cell Line, Tumor -; Cell Proliferation - drug effects; Cells, Cultured -; Chickens -; Chorioallantoic Membrane - drug effects; Chorioallantoic Membrane - physiology; Female -; Human Umbilical Vein Endothelial Cells -; Humans -; Lysophospholipids - metabolism; MAP Kinase Signaling System - drug effects; Neovascularization, Pathologic - drug therapy; Neovascularization, Pathologic - metabolism; Neovascularization, Pathologic - pathology; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - metabolism; Ovarian Neoplasms - pathology; Receptors, G-Protein-Coupled - agonists; Receptors, G-Protein-Coupled - metabolism; Stem Cells - drug effects; p38 Mitogen-Activated Protein Kinases - metabolism