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Aspirin and P2Y(12) inhibition attenuate platelet-induced ovarian cancer cell invasion

BACKGROUND: Platelet-cancer cell interactions play a key role in successful haematogenous metastasis. Disseminated malignancy is the leading cause of death among ovarian cancer patients. It is unknown why different ovarian cancers have different metastatic phenotypes. To investigate if platelet-canc...

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Autores principales: Cooke, Niamh M., Spillane, Cathy D., Sheils, Orla, O’Leary, John, Kenny, Dermot
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4565001/
https://www.ncbi.nlm.nih.gov/pubmed/26353776
http://dx.doi.org/10.1186/s12885-015-1634-x
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author Cooke, Niamh M.
Spillane, Cathy D.
Sheils, Orla
O’Leary, John
Kenny, Dermot
author_facet Cooke, Niamh M.
Spillane, Cathy D.
Sheils, Orla
O’Leary, John
Kenny, Dermot
author_sort Cooke, Niamh M.
collection PubMed
description BACKGROUND: Platelet-cancer cell interactions play a key role in successful haematogenous metastasis. Disseminated malignancy is the leading cause of death among ovarian cancer patients. It is unknown why different ovarian cancers have different metastatic phenotypes. To investigate if platelet-cancer cell interactions play a role, we characterized the response of ovarian cancer cell lines to platelets both functionally and at a molecular level. METHODS: Cell lines 59 M and SK-OV-3 were used as in vitro model systems of metastatic ovarian cancer. Platelet cloaking of each cell line was quantified by flow cytometry. Matrigel invasion chamber assays were used to assess the invasive capacity of the cell lines. The induction of an EMT was assessed by morphology analysis and by gene expression analysis of a panel of 11 EMT markers using TaqMan RT-PCR. RESULTS: SK-OV-3 cells adhered to and activated more platelets than 59 M cells (p = 0.0333). Platelets significantly promoted the ability of only SK-OV-3 cells to invade (p ≤ 0.0001). Morphology and transcritpome analysis indicated that platelets induce an epithelial-to-mesenchymal transition phenotype in both cells lines, with a more exaggerated response in SK-OV-3 cells. Next, we investigated if antiplatelet agents could abrogate the platelet-induced aggressive phenotype in SK-OV-3 cells. Both aspirin (p ≤ 0.05) and 2-methylthioadenosine 5′-monophosphate triethylammonium salt hydrate (P2Y(12) inhibitor; p ≤ 0.01) significantly decreased their invasion capacity, and effectively reverted invasion to levels comparable to SK-OV-3 cells alone. CONCLUSION: While there is increasing evidence for the cancer-protective effect of aspirin, this study suggests P2Y(12) inhibition may also play a role. Understanding these complex interactions between platelets and cancer cells could ultimately allow the establishment of therapies tailored to inhibiting metastasis, thus significantly reducing cancer morbidity.
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spelling pubmed-45650012015-09-11 Aspirin and P2Y(12) inhibition attenuate platelet-induced ovarian cancer cell invasion Cooke, Niamh M. Spillane, Cathy D. Sheils, Orla O’Leary, John Kenny, Dermot BMC Cancer Research Article BACKGROUND: Platelet-cancer cell interactions play a key role in successful haematogenous metastasis. Disseminated malignancy is the leading cause of death among ovarian cancer patients. It is unknown why different ovarian cancers have different metastatic phenotypes. To investigate if platelet-cancer cell interactions play a role, we characterized the response of ovarian cancer cell lines to platelets both functionally and at a molecular level. METHODS: Cell lines 59 M and SK-OV-3 were used as in vitro model systems of metastatic ovarian cancer. Platelet cloaking of each cell line was quantified by flow cytometry. Matrigel invasion chamber assays were used to assess the invasive capacity of the cell lines. The induction of an EMT was assessed by morphology analysis and by gene expression analysis of a panel of 11 EMT markers using TaqMan RT-PCR. RESULTS: SK-OV-3 cells adhered to and activated more platelets than 59 M cells (p = 0.0333). Platelets significantly promoted the ability of only SK-OV-3 cells to invade (p ≤ 0.0001). Morphology and transcritpome analysis indicated that platelets induce an epithelial-to-mesenchymal transition phenotype in both cells lines, with a more exaggerated response in SK-OV-3 cells. Next, we investigated if antiplatelet agents could abrogate the platelet-induced aggressive phenotype in SK-OV-3 cells. Both aspirin (p ≤ 0.05) and 2-methylthioadenosine 5′-monophosphate triethylammonium salt hydrate (P2Y(12) inhibitor; p ≤ 0.01) significantly decreased their invasion capacity, and effectively reverted invasion to levels comparable to SK-OV-3 cells alone. CONCLUSION: While there is increasing evidence for the cancer-protective effect of aspirin, this study suggests P2Y(12) inhibition may also play a role. Understanding these complex interactions between platelets and cancer cells could ultimately allow the establishment of therapies tailored to inhibiting metastasis, thus significantly reducing cancer morbidity. BioMed Central 2015-09-09 /pmc/articles/PMC4565001/ /pubmed/26353776 http://dx.doi.org/10.1186/s12885-015-1634-x Text en © Cooke et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Cooke, Niamh M.
Spillane, Cathy D.
Sheils, Orla
O’Leary, John
Kenny, Dermot
Aspirin and P2Y(12) inhibition attenuate platelet-induced ovarian cancer cell invasion
title Aspirin and P2Y(12) inhibition attenuate platelet-induced ovarian cancer cell invasion
title_full Aspirin and P2Y(12) inhibition attenuate platelet-induced ovarian cancer cell invasion
title_fullStr Aspirin and P2Y(12) inhibition attenuate platelet-induced ovarian cancer cell invasion
title_full_unstemmed Aspirin and P2Y(12) inhibition attenuate platelet-induced ovarian cancer cell invasion
title_short Aspirin and P2Y(12) inhibition attenuate platelet-induced ovarian cancer cell invasion
title_sort aspirin and p2y(12) inhibition attenuate platelet-induced ovarian cancer cell invasion
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4565001/
https://www.ncbi.nlm.nih.gov/pubmed/26353776
http://dx.doi.org/10.1186/s12885-015-1634-x
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