A role for L-alpha-lysophosphatidylinositol and GPR55 in the modulation of migration, orientation and polarization of human breast cancer cells

Lesley A. Ford, Anke J. Roelofs, Sharon Anavi-Goffer, Luisa Mowat, Daniel G. Simpson, Andrew J. Irving, Michael J. Rogers, Ann M. Rajnicek, Ruth A. Ross

    Research output: Contribution to journalArticlepeer-review

    103 Citations (Scopus)

    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 (R) 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 [35S]GTP gamma S 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.

    This article is part of a themed issue on Cannabinoids. To view the editorial for this themed issue visit http://dx.doi.org/10.1111/j.1476-5381.2010.00831.x.

    Original languageEnglish
    Pages (from-to)762-771
    Number of pages10
    JournalBritish Journal of Pharmacology
    Volume160
    Issue number3
    DOIs
    Publication statusPublished - Jun 2010

    Keywords

    • GPR55
    • GPCR
    • breast cancer
    • CBD
    • LPI
    • CANNABINOID RECEPTOR
    • CONTACT GUIDANCE
    • LYSOPHOSPHOLIPIDS
    • METASTASIS
    • ACTIVATION
    • PROTEINS
    • MECHANISMS
    • CARCINOMA
    • MOVEMENT
    • ADHESION

    Cite this