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Living in shear: platelets protect cancer cells from shear induced damage

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Abstract

Pharmacologically and genetically induced thrombocytopenia is associated with decreased metastasis, highlighting the importance of platelets in the bloodborne dissemination of cancer cells. It is frequently suggested that platelets support metastasis, in part, by protecting cancer cells from shear stress, a biomechanical force generated by blood flow. However, there is currently no evidence to support this hypothesis. To address this, we investigated the effect of shear stress on A2780 ovarian cancer cells in the presence and absence of platelets. Using a cone and plate viscometer, suspensions of A2780 cells with and without platelets were exposed to shear rates representing venous (200 s−1) and arterial (1,500 s−1) blood flow. Lactate dehydrogenase (LDH) release was used to quantify shear induced membrane damage. Both venous and arterial shear rates induced the release of LDH from A2780 cells, demonstrating their susceptibility to shear forces. In contrast, platelets released minimal levels of LDH in response to similar conditions. In the presence of platelets, there was a significant decrease in LDH release by A2780 cells under shear conditions, suggesting that platelets can confer protection against shear induced damage. The disruption of platelet–cancer cell interactions could increase the shear stress induced destruction of cancer cells in vivo.

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Acknowledgments

This research is supported through the National Biophotonics and Imaging Platform, Ireland, and funded by the Irish Government’s Programme for Research in Third Level Institutions, Cycle 4, and National Development Plan 2007–2013. NC is funded by a grant from Science Foundation Ireland (SFI) as part of the Biomedical Diagnostics Institute for Science Excellence and Technology (CSET), Grant Number: 10/CE/B1821.

Conflict of interest

The authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, 123 St Stephens Green, Dublin 2, Ireland

    Karl Egan, Niamh Cooke & Dermot Kenny

  2. Biomedical Diagnostics Institute, Dublin City University, Dublin, Ireland

    Karl Egan, Niamh Cooke & Dermot Kenny

Authors
  1. Karl Egan
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  2. Niamh Cooke
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  3. Dermot Kenny
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Correspondence to Dermot Kenny.

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Karl Egan and Niamh Cooke are joint first author

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Egan, K., Cooke, N. & Kenny, D. Living in shear: platelets protect cancer cells from shear induced damage. Clin Exp Metastasis 31, 697–704 (2014). https://doi.org/10.1007/s10585-014-9660-7

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  • DOI: https://doi.org/10.1007/s10585-014-9660-7

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