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)

Research output: Contribution to journalArticle

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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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Breast Neoplasms
MCF-7 Cells
Chemotaxis
Cell Movement
Serum
Cell Line
Tumor Microenvironment
G-Protein-Coupled Receptors
lysophosphatidylinositol
Small Interfering RNA
Neoplasms
Cell Membrane
Ligands
Polymerase Chain Reaction

Keywords

  • GPR55
  • GPCR
  • breast cancer
  • CBD
  • LPI

Cite this

A role for L-α-lysophosphatidylinositol and GPR55 in the modulation of migration, orientation and polarization of human breast cancer cells. / Ford, Lesley A; Roelofs, Anke J; Anavi-Goffer, Sharon; Mowat, Luisa; Simpson, Daniel G; Irving, Andrew J; Rogers, Michael J; Rajnicek, Ann M; Ross, Ruth A (Corresponding Author).

In: British Journal of Pharmacology, Vol. 160, No. 3, 06.2010, p. 762-771.

Research output: Contribution to journalArticle

Ford, Lesley A ; Roelofs, Anke J ; Anavi-Goffer, Sharon ; Mowat, Luisa ; Simpson, Daniel G ; Irving, Andrew J ; Rogers, Michael J ; Rajnicek, Ann M ; Ross, Ruth A. / A role for L-α-lysophosphatidylinositol and GPR55 in the modulation of migration, orientation and polarization of human breast cancer cells. In: British Journal of Pharmacology. 2010 ; Vol. 160, No. 3. pp. 762-771.
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T1 - A role for L-α-lysophosphatidylinositol and GPR55 in the modulation of migration, orientation and polarization of human breast cancer cells

AU - Ford, Lesley A

AU - Roelofs, Anke J

AU - Anavi-Goffer, Sharon

AU - Mowat, Luisa

AU - Simpson, Daniel G

AU - Irving, Andrew J

AU - Rogers, Michael J

AU - Rajnicek, Ann M

AU - Ross, Ruth A

PY - 2010/6

Y1 - 2010/6

N2 - 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.

AB - 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.

KW - GPR55

KW - GPCR

KW - breast cancer

KW - CBD

KW - LPI

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DO - 10.1111/j.1476-5381.2010.00743.x

M3 - Article

VL - 160

SP - 762

EP - 771

JO - British Journal of Pharmacology

JF - British Journal of Pharmacology

SN - 0007-1188

IS - 3

ER -