Expression Pattern of Purinergic Signaling Components in Colorectal Cancer Cells and Differential Cellular Outcomes Induced by Extracellular ATP and Adenosine

The purine nucleotide adenosine triphosphate (ATP) is known for its fundamental role in cellular bioenergetics. However, in the last decades, different works have described emerging functions for ATP, such as that of a danger signaling molecule acting in the extracellular space on both tumor and str...

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Autores principales:	Clémentine Dillard, Chloé Borde, Ammara Mohammad, Virginie Puchois, Laurent Jourdren, Annette K. Larsen, Michèle Sabbah, Vincent Maréchal, Alexandre E. Escargueil, Elodie Pramil
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	extracellular ATP 2D/3D cell culture purinergic receptors cell death induction cell cycle arrest Ca<sup>2+</sup> mobilization Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/574cd34048974f7bb0e0f83a21f776ec
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spelling	oai:doaj.org-article:574cd34048974f7bb0e0f83a21f776ec2021-11-11T16:56:12ZExpression Pattern of Purinergic Signaling Components in Colorectal Cancer Cells and Differential Cellular Outcomes Induced by Extracellular ATP and Adenosine10.3390/ijms2221114721422-00671661-6596https://doaj.org/article/574cd34048974f7bb0e0f83a21f776ec2021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11472https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067The purine nucleotide adenosine triphosphate (ATP) is known for its fundamental role in cellular bioenergetics. However, in the last decades, different works have described emerging functions for ATP, such as that of a danger signaling molecule acting in the extracellular space on both tumor and stromal compartments. Beside its role in immune cell signaling, several studies have shown that high concentrations of extracellular ATP can directly or indirectly act on cancer cells. Accordingly, it has been reported that purinergic receptors are widely expressed in tumor cells. However, their expression pattern is often associated with contradictory cellular outcomes. In this work, we first investigated gene expression profiles through “RNA-Sequencing” (RNA Seq) technology in four colorectal cancer (CRC) cell lines (HT29, LS513, LS174T, HCT116). Our results demonstrate that CRC cells mostly express the A2B, P2X4, P2Y1, P2Y2 and P2Y11 purinergic receptors. Among these, the P2Y1 and P2Y2 coding genes are markedly overexpressed in all CRC cells compared to the HCEC-1CT normal-like colonic cells. We then explored the cellular outcomes induced by extracellular ATP and adenosine. Our results show that in terms of cell death induction extracellular ATP is consistently more active than adenosine against CRC, while neither compound affected normal-like colonic cell survival. Intriguingly, while for the P2Y2 receptor pharmacological inhibition completely abolished the rise in cytoplasmic Ca<sup>2+</sup> observed after ATP exposure in all CRC cell lines, Ca<sup>2+</sup> mobilization only impacted the cellular outcome for HT29. In contrast, non-selective phosphodiesterase inhibition completely abolished the effects of extracellular ATP on CRC cells, suggesting that cAMP and/or cGMP levels might determine cellular outcome. Altogether, our study provides novel insights into the characterization of purinergic signaling in CRC.Clémentine DillardChloé BordeAmmara MohammadVirginie PuchoisLaurent JourdrenAnnette K. LarsenMichèle SabbahVincent MaréchalAlexandre E. EscargueilElodie PramilMDPI AGarticleextracellular ATP2D/3D cell culturepurinergic receptorscell death inductioncell cycle arrestCa<sup>2+</sup> mobilizationBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11472, p 11472 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	extracellular ATP 2D/3D cell culture purinergic receptors cell death induction cell cycle arrest Ca<sup>2+</sup> mobilization Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	extracellular ATP 2D/3D cell culture purinergic receptors cell death induction cell cycle arrest Ca<sup>2+</sup> mobilization Biology (General) QH301-705.5 Chemistry QD1-999 Clémentine Dillard Chloé Borde Ammara Mohammad Virginie Puchois Laurent Jourdren Annette K. Larsen Michèle Sabbah Vincent Maréchal Alexandre E. Escargueil Elodie Pramil Expression Pattern of Purinergic Signaling Components in Colorectal Cancer Cells and Differential Cellular Outcomes Induced by Extracellular ATP and Adenosine
description	The purine nucleotide adenosine triphosphate (ATP) is known for its fundamental role in cellular bioenergetics. However, in the last decades, different works have described emerging functions for ATP, such as that of a danger signaling molecule acting in the extracellular space on both tumor and stromal compartments. Beside its role in immune cell signaling, several studies have shown that high concentrations of extracellular ATP can directly or indirectly act on cancer cells. Accordingly, it has been reported that purinergic receptors are widely expressed in tumor cells. However, their expression pattern is often associated with contradictory cellular outcomes. In this work, we first investigated gene expression profiles through “RNA-Sequencing” (RNA Seq) technology in four colorectal cancer (CRC) cell lines (HT29, LS513, LS174T, HCT116). Our results demonstrate that CRC cells mostly express the A2B, P2X4, P2Y1, P2Y2 and P2Y11 purinergic receptors. Among these, the P2Y1 and P2Y2 coding genes are markedly overexpressed in all CRC cells compared to the HCEC-1CT normal-like colonic cells. We then explored the cellular outcomes induced by extracellular ATP and adenosine. Our results show that in terms of cell death induction extracellular ATP is consistently more active than adenosine against CRC, while neither compound affected normal-like colonic cell survival. Intriguingly, while for the P2Y2 receptor pharmacological inhibition completely abolished the rise in cytoplasmic Ca<sup>2+</sup> observed after ATP exposure in all CRC cell lines, Ca<sup>2+</sup> mobilization only impacted the cellular outcome for HT29. In contrast, non-selective phosphodiesterase inhibition completely abolished the effects of extracellular ATP on CRC cells, suggesting that cAMP and/or cGMP levels might determine cellular outcome. Altogether, our study provides novel insights into the characterization of purinergic signaling in CRC.
format	article
author	Clémentine Dillard Chloé Borde Ammara Mohammad Virginie Puchois Laurent Jourdren Annette K. Larsen Michèle Sabbah Vincent Maréchal Alexandre E. Escargueil Elodie Pramil
author_facet	Clémentine Dillard Chloé Borde Ammara Mohammad Virginie Puchois Laurent Jourdren Annette K. Larsen Michèle Sabbah Vincent Maréchal Alexandre E. Escargueil Elodie Pramil
author_sort	Clémentine Dillard
title	Expression Pattern of Purinergic Signaling Components in Colorectal Cancer Cells and Differential Cellular Outcomes Induced by Extracellular ATP and Adenosine
title_short	Expression Pattern of Purinergic Signaling Components in Colorectal Cancer Cells and Differential Cellular Outcomes Induced by Extracellular ATP and Adenosine
title_full	Expression Pattern of Purinergic Signaling Components in Colorectal Cancer Cells and Differential Cellular Outcomes Induced by Extracellular ATP and Adenosine
title_fullStr	Expression Pattern of Purinergic Signaling Components in Colorectal Cancer Cells and Differential Cellular Outcomes Induced by Extracellular ATP and Adenosine
title_full_unstemmed	Expression Pattern of Purinergic Signaling Components in Colorectal Cancer Cells and Differential Cellular Outcomes Induced by Extracellular ATP and Adenosine
title_sort	expression pattern of purinergic signaling components in colorectal cancer cells and differential cellular outcomes induced by extracellular atp and adenosine
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/574cd34048974f7bb0e0f83a21f776ec
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Expression Pattern of Purinergic Signaling Components in Colorectal Cancer Cells and Differential Cellular Outcomes Induced by Extracellular ATP and Adenosine

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