GPR55-Mediated Effects in Colon Cancer Cell Lines

Carina Hasenoehrl; David Feuersinger; Melanie Kienzl; Rudolf Schicho

doi:10.1159/000496356

GPR55-Mediated Effects in Colon Cancer Cell Lines

Med Cannabis Cannabinoids. 2019 Feb 22;2(1):22-28. doi: 10.1159/000496356. eCollection 2019 Sep.

Authors

Carina Hasenoehrl¹, David Feuersinger¹, Melanie Kienzl^{1

2}, Rudolf Schicho^{1

2}

Affiliations

¹ Division of Pharmacology, Otto Loewi Research Center, Medical University of Graz, Graz, Austria.
² BioTechMed, Graz, Austria.

Abstract

The cannabinoid-responsive G protein-coupled receptor GPR55 and its endogenous ligand L-α-lysophosphatidyl-inositol (LPI) have been reported to play a role in several cancers. A proliferation-enhancing effect of GPR55 has been described for several cancer cell lines and LPI has been found elevated in cancer patients. The aim of this study was to investigate whether GPR55 signaling had an effect on the proliferation of colon cancer cell lines. Using cell viability assays and Western blotting, we show that stable overexpression of the GPR55 receptor led to a growth advantage of SW480 cells per se. Proliferation of native colon cancer cell lines, however, was not affected by pharmacological manipulation of GPR55. Interestingly though, GPR55 signaling was responsive to treatment with both the GPR55 agonist LPI and the antagonist CID16020046 in the overexpressing cancer cell lines. This was evident through significantly increased or decreased levels of phosphorylated ERK1/2, respectively. Taken together, our findings suggest that GPR55 is constitutively activated in overexpressing colon cancer cells affecting ERK1/2 phosphorylation and cell proliferation.

Keywords: Cannabinoids; Colorectal cancer; GPR55; Lysophosphatidylinositol.