CD73 facilitates EMT progression and promotes lung metastases in triple-negative breast cancer

Abstract CD73 is a cell surface ecto-5′-nucleotidase, which converts extracellular adenosine monophosphate to adenosine. High tumor CD73 expression is associated with poor outcome among triple-negative breast cancer (TNBC) patients. Here we investigated the mechanisms by which CD73 might contribute...

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Autores principales:	Nataliia Petruk, Sanni Tuominen, Malin Åkerfelt, Jesse Mattsson, Jouko Sandholm, Matthias Nees, Gennady G. Yegutkin, Arja Jukkola, Johanna Tuomela, Katri S. Selander
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b2c631e7001b40c2910848b8522fac2a
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spelling	oai:doaj.org-article:b2c631e7001b40c2910848b8522fac2a2021-12-02T17:05:11ZCD73 facilitates EMT progression and promotes lung metastases in triple-negative breast cancer10.1038/s41598-021-85379-z2045-2322https://doaj.org/article/b2c631e7001b40c2910848b8522fac2a2021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-85379-zhttps://doaj.org/toc/2045-2322Abstract CD73 is a cell surface ecto-5′-nucleotidase, which converts extracellular adenosine monophosphate to adenosine. High tumor CD73 expression is associated with poor outcome among triple-negative breast cancer (TNBC) patients. Here we investigated the mechanisms by which CD73 might contribute to TNBC progression. This was done by inhibiting CD73 with adenosine 5′-(α, β-methylene) diphosphate (APCP) in MDA-MB-231 or 4T1 TNBC cells or through shRNA-silencing (sh-CD73). Effects of such inhibition on cell behavior was then studied in normoxia and hypoxia in vitro and in an orthotopic mouse model in vivo. CD73 inhibition, through shRNA or APCP significantly decreased cellular viability and migration in normoxia. Inhibition of CD73 also resulted in suppression of hypoxia-induced increase in viability and prevented cell protrusion elongation in both normoxia and hypoxia in cancer cells. Sh-CD73 4T1 cells formed significantly smaller and less invasive 3D organoids in vitro, and significantly smaller orthotopic tumors and less lung metastases than control shRNA cells in vivo. CD73 suppression increased E-cadherin and decreased vimentin expression in vitro and in vivo, proposing maintenance of a more epithelial phenotype. In conclusion, our results suggest that CD73 may promote early steps of tumor progression, possibly through facilitating epithelial–mesenchymal transition.Nataliia PetrukSanni TuominenMalin ÅkerfeltJesse MattssonJouko SandholmMatthias NeesGennady G. YegutkinArja JukkolaJohanna TuomelaKatri S. SelanderNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nataliia Petruk Sanni Tuominen Malin Åkerfelt Jesse Mattsson Jouko Sandholm Matthias Nees Gennady G. Yegutkin Arja Jukkola Johanna Tuomela Katri S. Selander CD73 facilitates EMT progression and promotes lung metastases in triple-negative breast cancer
description	Abstract CD73 is a cell surface ecto-5′-nucleotidase, which converts extracellular adenosine monophosphate to adenosine. High tumor CD73 expression is associated with poor outcome among triple-negative breast cancer (TNBC) patients. Here we investigated the mechanisms by which CD73 might contribute to TNBC progression. This was done by inhibiting CD73 with adenosine 5′-(α, β-methylene) diphosphate (APCP) in MDA-MB-231 or 4T1 TNBC cells or through shRNA-silencing (sh-CD73). Effects of such inhibition on cell behavior was then studied in normoxia and hypoxia in vitro and in an orthotopic mouse model in vivo. CD73 inhibition, through shRNA or APCP significantly decreased cellular viability and migration in normoxia. Inhibition of CD73 also resulted in suppression of hypoxia-induced increase in viability and prevented cell protrusion elongation in both normoxia and hypoxia in cancer cells. Sh-CD73 4T1 cells formed significantly smaller and less invasive 3D organoids in vitro, and significantly smaller orthotopic tumors and less lung metastases than control shRNA cells in vivo. CD73 suppression increased E-cadherin and decreased vimentin expression in vitro and in vivo, proposing maintenance of a more epithelial phenotype. In conclusion, our results suggest that CD73 may promote early steps of tumor progression, possibly through facilitating epithelial–mesenchymal transition.
format	article
author	Nataliia Petruk Sanni Tuominen Malin Åkerfelt Jesse Mattsson Jouko Sandholm Matthias Nees Gennady G. Yegutkin Arja Jukkola Johanna Tuomela Katri S. Selander
author_facet	Nataliia Petruk Sanni Tuominen Malin Åkerfelt Jesse Mattsson Jouko Sandholm Matthias Nees Gennady G. Yegutkin Arja Jukkola Johanna Tuomela Katri S. Selander
author_sort	Nataliia Petruk
title	CD73 facilitates EMT progression and promotes lung metastases in triple-negative breast cancer
title_short	CD73 facilitates EMT progression and promotes lung metastases in triple-negative breast cancer
title_full	CD73 facilitates EMT progression and promotes lung metastases in triple-negative breast cancer
title_fullStr	CD73 facilitates EMT progression and promotes lung metastases in triple-negative breast cancer
title_full_unstemmed	CD73 facilitates EMT progression and promotes lung metastases in triple-negative breast cancer
title_sort	cd73 facilitates emt progression and promotes lung metastases in triple-negative breast cancer
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/b2c631e7001b40c2910848b8522fac2a
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CD73 facilitates EMT progression and promotes lung metastases in triple-negative breast cancer

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