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Title: The pharmacology of GPR55 and its potential role in cancer
Author: Ford, Lesley
ISNI:       0000 0004 2677 6835
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 2009
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In a recent patent, GPR55 emerged as a novel target for cannabinoid modulation, and was found to be activated by a number of synthetic and endogenous cannabinoids, including anandamide, virodhamine, and AM251.  There is mounting evidence to suggest that cannabinoids play a role in tumour progression.  The potential role of GPR55 in cancer, however, remains to be explored. This study used qPCR to determine GPR55, CB1 and CB2 expression levels in a number of native breast cancer cell lines, and found that GPR55 was expressed in highly metastatic cells, including MDA-MB-231 and B02-GFP cell lines. Studies into the modulation of GPR55 by its suggested ligands showed that agonist L-α-lysophosphatidylinositol enhanced the migration of metastatic breast cancer cells, and augmented certain behaviours associated with a more aggressive phenotype, including enhancing the ability of these cells to orientate and polarise in response to grooved substratum.  Meanwhile the GPR55 antagonist CBD inhibited the migration and invasion of these cells.  Using over-expression and siRNA knockdown of GPR55, we have implicated this receptor in both the LPI- and CBD-mediated effects on migration/invasion.  Furthermore, we found that LPI significantly stimulated both RhoA activation, and ERK1/2 phosphorylation in hGPR55-expressing HEK293 cells, but not in untransfected HEK293 cells.  These studies highlight an important role for GPR55 as a new biomarker in cancer, and suggest a possible therapeutic role for cannabinoids in the treatment of metastasis.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Cannabinoids ; Tumors ; Cancer