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CD73/Adenosine Pathway Involvement in the Interaction of Non-Small Cell Lung Cancer Stem Cells and Bone Cells in the Pre-Metastatic Niche

Adenosinergic signaling is an important regulator of tissue homeostasis and extracellular accumulation of adenosine (Ado) and is associated with different pathologies, such as cancer. In non-small-cell lung cancer (NSCLC), a subset of CD133/CXCR4+ cancer stem cell (CSCs) has been demonstrated to ini...

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Autores principales: Bertolini, Giulia, Compagno, Mara, Belisario, Dimas Carolina, Bracci, Cristiano, Genova, Tullio, Mussano, Federico, Vitale, Massimo, Horenstein, Alberto, Malavasi, Fabio, Ferracini, Riccardo, Roato, Ilaria
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9104817/
https://www.ncbi.nlm.nih.gov/pubmed/35563517
http://dx.doi.org/10.3390/ijms23095126
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author Bertolini, Giulia
Compagno, Mara
Belisario, Dimas Carolina
Bracci, Cristiano
Genova, Tullio
Mussano, Federico
Vitale, Massimo
Horenstein, Alberto
Malavasi, Fabio
Ferracini, Riccardo
Roato, Ilaria
author_facet Bertolini, Giulia
Compagno, Mara
Belisario, Dimas Carolina
Bracci, Cristiano
Genova, Tullio
Mussano, Federico
Vitale, Massimo
Horenstein, Alberto
Malavasi, Fabio
Ferracini, Riccardo
Roato, Ilaria
author_sort Bertolini, Giulia
collection PubMed
description Adenosinergic signaling is an important regulator of tissue homeostasis and extracellular accumulation of adenosine (Ado) and is associated with different pathologies, such as cancer. In non-small-cell lung cancer (NSCLC), a subset of CD133/CXCR4+ cancer stem cell (CSCs) has been demonstrated to initiate bone metastases. Here we investigated how NSCLC CSCs interact with osteoclasts (OCs) and osteoblasts (OBs) by modulating Ado production and OC activity. We proved that CSC-spheres, generated in vitro from NSCLC cell lines, express CD38, PC-1, and CD73, enzymes of the non-canonical adenosinergic pathway, produce high level of Ado, and down-regulate A1R and A3R inhibitory receptors, while expressing A2AR and A2BR. To address the Ado role and modulation of the in-bone pre-metastatic niche, we performed co-cultures of CSC-spheres with OCs and OBs cells. Firstly, we verified that active OCs do not activate non-canonical the adenosinergic pathway, conversely to OBs. OCs co-cultured with CSC-spheres increase Ado production that is related to the OC resorption activity and contributes to T-cell suppression. Finally, we proved the efficacy of anti-CD73 agents in blocking NSCLC cell migration. Overall, we assessed the importance of adenosinergic signaling in the interaction between CSCs and OCs at the pre-metastatic niche, with therapeutic implications related to Ado production.
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spelling pubmed-91048172022-05-14 CD73/Adenosine Pathway Involvement in the Interaction of Non-Small Cell Lung Cancer Stem Cells and Bone Cells in the Pre-Metastatic Niche Bertolini, Giulia Compagno, Mara Belisario, Dimas Carolina Bracci, Cristiano Genova, Tullio Mussano, Federico Vitale, Massimo Horenstein, Alberto Malavasi, Fabio Ferracini, Riccardo Roato, Ilaria Int J Mol Sci Article Adenosinergic signaling is an important regulator of tissue homeostasis and extracellular accumulation of adenosine (Ado) and is associated with different pathologies, such as cancer. In non-small-cell lung cancer (NSCLC), a subset of CD133/CXCR4+ cancer stem cell (CSCs) has been demonstrated to initiate bone metastases. Here we investigated how NSCLC CSCs interact with osteoclasts (OCs) and osteoblasts (OBs) by modulating Ado production and OC activity. We proved that CSC-spheres, generated in vitro from NSCLC cell lines, express CD38, PC-1, and CD73, enzymes of the non-canonical adenosinergic pathway, produce high level of Ado, and down-regulate A1R and A3R inhibitory receptors, while expressing A2AR and A2BR. To address the Ado role and modulation of the in-bone pre-metastatic niche, we performed co-cultures of CSC-spheres with OCs and OBs cells. Firstly, we verified that active OCs do not activate non-canonical the adenosinergic pathway, conversely to OBs. OCs co-cultured with CSC-spheres increase Ado production that is related to the OC resorption activity and contributes to T-cell suppression. Finally, we proved the efficacy of anti-CD73 agents in blocking NSCLC cell migration. Overall, we assessed the importance of adenosinergic signaling in the interaction between CSCs and OCs at the pre-metastatic niche, with therapeutic implications related to Ado production. MDPI 2022-05-04 /pmc/articles/PMC9104817/ /pubmed/35563517 http://dx.doi.org/10.3390/ijms23095126 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bertolini, Giulia
Compagno, Mara
Belisario, Dimas Carolina
Bracci, Cristiano
Genova, Tullio
Mussano, Federico
Vitale, Massimo
Horenstein, Alberto
Malavasi, Fabio
Ferracini, Riccardo
Roato, Ilaria
CD73/Adenosine Pathway Involvement in the Interaction of Non-Small Cell Lung Cancer Stem Cells and Bone Cells in the Pre-Metastatic Niche
title CD73/Adenosine Pathway Involvement in the Interaction of Non-Small Cell Lung Cancer Stem Cells and Bone Cells in the Pre-Metastatic Niche
title_full CD73/Adenosine Pathway Involvement in the Interaction of Non-Small Cell Lung Cancer Stem Cells and Bone Cells in the Pre-Metastatic Niche
title_fullStr CD73/Adenosine Pathway Involvement in the Interaction of Non-Small Cell Lung Cancer Stem Cells and Bone Cells in the Pre-Metastatic Niche
title_full_unstemmed CD73/Adenosine Pathway Involvement in the Interaction of Non-Small Cell Lung Cancer Stem Cells and Bone Cells in the Pre-Metastatic Niche
title_short CD73/Adenosine Pathway Involvement in the Interaction of Non-Small Cell Lung Cancer Stem Cells and Bone Cells in the Pre-Metastatic Niche
title_sort cd73/adenosine pathway involvement in the interaction of non-small cell lung cancer stem cells and bone cells in the pre-metastatic niche
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9104817/
https://www.ncbi.nlm.nih.gov/pubmed/35563517
http://dx.doi.org/10.3390/ijms23095126
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