Journal article
Adenosine arrests breast cancer cell motility by A3 receptor stimulation
Purinergic signalling, Vol.12(4), pp.673-685
12/2016
DOI: 10.1007/s11302-016-9531-6
PMCID: PMC5124008
PMID: 27577957
Abstract
In neutrophils, adenosine triphosphate (ATP) release and autocrine purinergic signaling regulate coordinated cell motility during chemotaxis. Here, we studied whether similar mechanisms regulate the motility of breast cancer cells. While neutrophils and benign human mammary epithelial cells (HMEC) form a single leading edge, MDA-MB-231 breast cancer cells possess multiple leading edges enriched with A3 adenosine receptors. Compared to HMEC, MDA-MB-231 cells overexpress the ectonucleotidases ENPP1 and CD73, which convert extracellular ATP released by the cells to adenosine that stimulates A3 receptors and promotes cell migration with frequent directional changes. However, exogenous adenosine added to breast cancer cells or the A3 receptor agonist IB-MECA dose-dependently arrested cell motility by simultaneous stimulation of multiple leading edges, doubling cell surface areas and significantly reducing migration velocity by up to 75 %. We conclude that MDA-MB-231 cells, HMEC, and neutrophils differ in the purinergic signaling mechanisms that regulate their motility patterns and that the subcellular distribution of A3 adenosine receptors in MDA-MB-231 breast cancer cells contributes to dysfunctional cell motility. These findings imply that purinergic signaling mechanisms may be potential therapeutic targets to interfere with the motility of breast cancer cells in order to reduce the spread of cancer cells and the risk of metastasis.
Details
- Title: Subtitle
- Adenosine arrests breast cancer cell motility by A3 receptor stimulation
- Creators
- Carola Ledderose - Department of Surgery, Beth Israel Deaconess Medical Center Harvard Medical School 330 Brookline Avenue Boston MA 02215 USAMarco Hefti - Department of Surgery, Beth Israel Deaconess Medical Center Harvard Medical School 330 Brookline Avenue Boston MA 02215 USAYu Chen - Department of Surgery, Beth Israel Deaconess Medical Center Harvard Medical School 330 Brookline Avenue Boston MA 02215 USAYi Bao - Department of Surgery, Beth Israel Deaconess Medical Center Harvard Medical School 330 Brookline Avenue Boston MA 02215 USAThomas Seier - Department of Surgery, Beth Israel Deaconess Medical Center Harvard Medical School 330 Brookline Avenue Boston MA 02215 USALinglin Li - Department of Surgery, Beth Israel Deaconess Medical Center Harvard Medical School 330 Brookline Avenue Boston MA 02215 USATobias Woehrle - Department of Surgery, Beth Israel Deaconess Medical Center Harvard Medical School 330 Brookline Avenue Boston MA 02215 USAJingping Zhang - Department of Surgery, Beth Israel Deaconess Medical Center Harvard Medical School 330 Brookline Avenue Boston MA 02215 USAWolfgang Junger - Ludwig Boltzmann Institute for Traumatology Vienna 1200 Austria
- Resource Type
- Journal article
- Publication Details
- Purinergic signalling, Vol.12(4), pp.673-685
- Publisher
- Springer Netherlands; Dordrecht
- DOI
- 10.1007/s11302-016-9531-6
- PMID
- 27577957
- PMCID
- PMC5124008
- ISSN
- 1573-9538
- eISSN
- 1573-9546
- Grant note
- AI-080582; T32 GM-103702 / National Institutes of Health (http://dx.doi.org/10.13039/100000002) LE-3209/1-1 / DFG
- Language
- English
- Date published
- 12/2016
- Academic Unit
- Pathology; Iowa Neuroscience Institute
- Record Identifier
- 9984046916602771
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