A role for L-α-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 (Corresponding Author)

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Abstract

Background and purpose:  Increased circulating levels of L-α-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 [35S]GTPγS to cell membranes (pEC50 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.
Original languageEnglish
Pages (from-to)762-771
Number of pages10
JournalBritish Journal of Pharmacology
Volume160
Issue number3
Early online date11 Mar 2010
DOIs
Publication statusPublished - Jun 2010

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Keywords

  • GPR55
  • GPCR
  • breast cancer
  • CBD
  • LPI

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