A role for L-α-lysophosphatidylinositol and GPR55 in the modulation of migration, orientation and polarization of human breast cancer cells
In: Cannabinoids, Jg. 160 (2010), Heft 3, S. 762-771
Online
academicJournal
- print, 3/4 p
Zugriff:
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.
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A role for L-α-lysophosphatidylinositol and GPR55 in the modulation of migration, orientation and polarization of human breast cancer cells
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Autor/in / Beteiligte Person: | 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 |
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Zeitschrift: | Cannabinoids, Jg. 160 (2010), Heft 3, S. 762-771 |
Veröffentlichung: | Basingstoke: Nature Publishing Group, 2010 |
Medientyp: | academicJournal |
Umfang: | print, 3/4 p |
ISSN: | 0007-1188 (print) |
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