Julie Gardener
New Member
A Role for L-alpha-lysophosphatidylinositol and GPR55 in the Modulation of migration, Orientation and Polarization of Human Breast Cancer Cells.
Ford LA, Roelofs AJ, Anavi-Goffer S, Mowat L, Simpson DG, Irving AJ, Rogers MJ, Rajnicek AM, Ross RA.Source
School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK.
Br J Pharmacol. 2010 Jun;160(3):762-71.
Abstract
BACKGROUND AND PURPOSE:
Increased circulating levels of L-alpha-lysophosphatidylinositol (LPI) are associated with cancer and LPI is a potent, ligand for the G-protein-coupled receptor GPR55. Here we have assessed the modulation of breast cancer cell migration, orientation and polarization by LPI and GPR55.
EXPERIMENTAL APPROACH:
Quantitative RT-PCR was used to measure GPR55 expression in breast cancer cell lines. Cell migration and invasion were measured using a Boyden chamber chemotaxis assay and Cultrex invasion assay, respectively. Cell polarization and orientation in response to the microenvironment were measured using slides containing nanometric grooves.
KEY RESULTS:
GPR55 expression was detected in the highly metastatic MDA-MB-231 breast cancer cell line. In these cells, LPI stimulated binding of [(35)S]GTPgammaS to cell membranes (pEC(50) 6.47 +/- 0.45) and significantly enhanced cell chemotaxis towards serum. MCF-7 cells expressed low levels of GPR55 and did not migrate or invade towards serum factors. When GPR55 was over-expressed in MCF-7 cells, serum induced a robust migratory and invasive response, which was further enhanced by LPI and prevented by siRNA to GPR55. The physical microenvironment has been identified as a key factor in determining breast tumour cell metastatic fate. LPI endowed MDA-MB-231 cells with the capacity to detect shallow (40 nm deep) grooved slides and induced marked cancer cell polarization on both flat and grooved surfaces.
CONCLUSIONS AND IMPLICATIONS:
LPI and GPR55 play a role in the modulation of migration, orientation and polarization of breast cancer cells in response to the tumour microenvironment.
PMID: 20590578 [PubMed - indexed for MEDLINE] PMCID: PMC2931574
Source: A role for L-alpha-lysophosphatidylinositol and GP... [Br J Pharmacol. 2010] - PubMed result
