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ECM Composition Differentially Regulates Intracellular and Extracellular pH in Normal and Cancer Pancreatic Duct Epithelial Cells
Intracellular pH (pHi) regulation is a challenge for the exocrine pancreas, where the luminal secretion of bicarbonate-rich fluid is accompanied by interstitial flows of acid. This acid–base transport requires a plethora of ion transporters, including bicarbonate transporters and the Na(+)/H(+) exch...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10341693/ https://www.ncbi.nlm.nih.gov/pubmed/37445810 http://dx.doi.org/10.3390/ijms241310632 |
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author | Di Molfetta, Daria Cannone, Stefania Greco, Maria Raffaella Caroppo, Rosa Piccapane, Francesca Carvalho, Tiago Miguel Amaral Altamura, Concetta Saltarella, Ilaria Tavares Valente, Diana Desaphy, Jean Francois Reshkin, Stephan J. Cardone, Rosa Angela |
author_facet | Di Molfetta, Daria Cannone, Stefania Greco, Maria Raffaella Caroppo, Rosa Piccapane, Francesca Carvalho, Tiago Miguel Amaral Altamura, Concetta Saltarella, Ilaria Tavares Valente, Diana Desaphy, Jean Francois Reshkin, Stephan J. Cardone, Rosa Angela |
author_sort | Di Molfetta, Daria |
collection | PubMed |
description | Intracellular pH (pHi) regulation is a challenge for the exocrine pancreas, where the luminal secretion of bicarbonate-rich fluid is accompanied by interstitial flows of acid. This acid–base transport requires a plethora of ion transporters, including bicarbonate transporters and the Na(+)/H(+) exchanger isoform 1 (NHE1), which are dysregulated in Pancreatic Ductal Adenocarcinoma (PDAC). PDAC progression is favored by a Collagen-I rich extracellular matrix (ECM) which exacerbates the physiological interstitial acidosis. In organotypic cultures of normal human pancreatic cells (HPDE), parenchymal cancer cells (CPCs) and cancer stem cells (CSCs) growing on matrices reproducing ECM changes during progression, we studied resting pHi, the pHi response to fluxes of NaHCO(3) and acidosis and the role of NHE1 in pHi regulation. Our findings show that: (i) on the physiological ECM, HPDE cells have the most alkaline pHi, followed by CSCs and CPCs, while a Collagen I-rich ECM reverses the acid–base balance in cancer cells compared to normal cells; (ii) both resting pHi and pHi recovery from an acid load are reduced by extracellular NaHCO(3), especially in HPDE cells on a normal ECM; (iii) cancer cell NHE1 activity is less affected by NaHCO(3). We conclude that ECM composition and the fluctuations of pHe cooperate to predispose pHi homeostasis towards the presence of NaHCO(3) gradients similar to that expected in the tumor. |
format | Online Article Text |
id | pubmed-10341693 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-103416932023-07-14 ECM Composition Differentially Regulates Intracellular and Extracellular pH in Normal and Cancer Pancreatic Duct Epithelial Cells Di Molfetta, Daria Cannone, Stefania Greco, Maria Raffaella Caroppo, Rosa Piccapane, Francesca Carvalho, Tiago Miguel Amaral Altamura, Concetta Saltarella, Ilaria Tavares Valente, Diana Desaphy, Jean Francois Reshkin, Stephan J. Cardone, Rosa Angela Int J Mol Sci Article Intracellular pH (pHi) regulation is a challenge for the exocrine pancreas, where the luminal secretion of bicarbonate-rich fluid is accompanied by interstitial flows of acid. This acid–base transport requires a plethora of ion transporters, including bicarbonate transporters and the Na(+)/H(+) exchanger isoform 1 (NHE1), which are dysregulated in Pancreatic Ductal Adenocarcinoma (PDAC). PDAC progression is favored by a Collagen-I rich extracellular matrix (ECM) which exacerbates the physiological interstitial acidosis. In organotypic cultures of normal human pancreatic cells (HPDE), parenchymal cancer cells (CPCs) and cancer stem cells (CSCs) growing on matrices reproducing ECM changes during progression, we studied resting pHi, the pHi response to fluxes of NaHCO(3) and acidosis and the role of NHE1 in pHi regulation. Our findings show that: (i) on the physiological ECM, HPDE cells have the most alkaline pHi, followed by CSCs and CPCs, while a Collagen I-rich ECM reverses the acid–base balance in cancer cells compared to normal cells; (ii) both resting pHi and pHi recovery from an acid load are reduced by extracellular NaHCO(3), especially in HPDE cells on a normal ECM; (iii) cancer cell NHE1 activity is less affected by NaHCO(3). We conclude that ECM composition and the fluctuations of pHe cooperate to predispose pHi homeostasis towards the presence of NaHCO(3) gradients similar to that expected in the tumor. MDPI 2023-06-25 /pmc/articles/PMC10341693/ /pubmed/37445810 http://dx.doi.org/10.3390/ijms241310632 Text en © 2023 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 Di Molfetta, Daria Cannone, Stefania Greco, Maria Raffaella Caroppo, Rosa Piccapane, Francesca Carvalho, Tiago Miguel Amaral Altamura, Concetta Saltarella, Ilaria Tavares Valente, Diana Desaphy, Jean Francois Reshkin, Stephan J. Cardone, Rosa Angela ECM Composition Differentially Regulates Intracellular and Extracellular pH in Normal and Cancer Pancreatic Duct Epithelial Cells |
title | ECM Composition Differentially Regulates Intracellular and Extracellular pH in Normal and Cancer Pancreatic Duct Epithelial Cells |
title_full | ECM Composition Differentially Regulates Intracellular and Extracellular pH in Normal and Cancer Pancreatic Duct Epithelial Cells |
title_fullStr | ECM Composition Differentially Regulates Intracellular and Extracellular pH in Normal and Cancer Pancreatic Duct Epithelial Cells |
title_full_unstemmed | ECM Composition Differentially Regulates Intracellular and Extracellular pH in Normal and Cancer Pancreatic Duct Epithelial Cells |
title_short | ECM Composition Differentially Regulates Intracellular and Extracellular pH in Normal and Cancer Pancreatic Duct Epithelial Cells |
title_sort | ecm composition differentially regulates intracellular and extracellular ph in normal and cancer pancreatic duct epithelial cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10341693/ https://www.ncbi.nlm.nih.gov/pubmed/37445810 http://dx.doi.org/10.3390/ijms241310632 |
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