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<sup<+&...
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Autor*in:	Daria Di Molfetta [verfasserIn] Stefania Cannone [verfasserIn] Maria Raffaella Greco [verfasserIn] Rosa Caroppo [verfasserIn] Francesca Piccapane [verfasserIn] Tiago Miguel Amaral Carvalho [verfasserIn] Concetta Altamura [verfasserIn] Ilaria Saltarella [verfasserIn] Diana Tavares Valente [verfasserIn] Jean Francois Desaphy [verfasserIn] Stephan J. Reshkin [verfasserIn] Rosa Angela Cardone [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2023

Schlagwörter:	PDAC NHE1 bicarbonate transport

Übergeordnetes Werk:	In: International Journal of Molecular Sciences - MDPI AG, 2003, 24(2023), 13, p 10632
Übergeordnetes Werk:	volume:24 ; year:2023 ; number:13, p 10632

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc Journal toc

DOI / URN:	10.3390/ijms241310632

Katalog-ID:	DOAJ094011702

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allfields	10.3390/ijms241310632 doi (DE-627)DOAJ094011702 (DE-599)DOAJb90c6326b4ed44adad9ec93fff63272a DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Daria Di Molfetta verfasserin aut ECM Composition Differentially Regulates Intracellular and Extracellular pH in Normal and Cancer Pancreatic Duct Epithelial Cells 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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<sup<+</sup</H<sup<+</sup< 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<sub<3</sub< 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<sub<3</sub<, especially in HPDE cells on a normal ECM; (iii) cancer cell NHE1 activity is less affected by NaHCO<sub<3</sub<. We conclude that ECM composition and the fluctuations of pHe cooperate to predispose pHi homeostasis towards the presence of NaHCO<sub<3</sub< gradients similar to that expected in the tumor. PDAC NHE1 bicarbonate transport Biology (General) Chemistry Stefania Cannone verfasserin aut Maria Raffaella Greco verfasserin aut Rosa Caroppo verfasserin aut Francesca Piccapane verfasserin aut Tiago Miguel Amaral Carvalho verfasserin aut Concetta Altamura verfasserin aut Ilaria Saltarella verfasserin aut Diana Tavares Valente verfasserin aut Jean Francois Desaphy verfasserin aut Stephan J. Reshkin verfasserin aut Rosa Angela Cardone verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 24(2023), 13, p 10632 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:24 year:2023 number:13, p 10632 https://doi.org/10.3390/ijms241310632 kostenfrei https://doaj.org/article/b90c6326b4ed44adad9ec93fff63272a kostenfrei https://www.mdpi.com/1422-0067/24/13/10632 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 24 2023 13, p 10632
spelling	10.3390/ijms241310632 doi (DE-627)DOAJ094011702 (DE-599)DOAJb90c6326b4ed44adad9ec93fff63272a DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Daria Di Molfetta verfasserin aut ECM Composition Differentially Regulates Intracellular and Extracellular pH in Normal and Cancer Pancreatic Duct Epithelial Cells 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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<sup<+</sup</H<sup<+</sup< 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<sub<3</sub< 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<sub<3</sub<, especially in HPDE cells on a normal ECM; (iii) cancer cell NHE1 activity is less affected by NaHCO<sub<3</sub<. We conclude that ECM composition and the fluctuations of pHe cooperate to predispose pHi homeostasis towards the presence of NaHCO<sub<3</sub< gradients similar to that expected in the tumor. PDAC NHE1 bicarbonate transport Biology (General) Chemistry Stefania Cannone verfasserin aut Maria Raffaella Greco verfasserin aut Rosa Caroppo verfasserin aut Francesca Piccapane verfasserin aut Tiago Miguel Amaral Carvalho verfasserin aut Concetta Altamura verfasserin aut Ilaria Saltarella verfasserin aut Diana Tavares Valente verfasserin aut Jean Francois Desaphy verfasserin aut Stephan J. Reshkin verfasserin aut Rosa Angela Cardone verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 24(2023), 13, p 10632 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:24 year:2023 number:13, p 10632 https://doi.org/10.3390/ijms241310632 kostenfrei https://doaj.org/article/b90c6326b4ed44adad9ec93fff63272a kostenfrei https://www.mdpi.com/1422-0067/24/13/10632 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 24 2023 13, p 10632
allfields_unstemmed	10.3390/ijms241310632 doi (DE-627)DOAJ094011702 (DE-599)DOAJb90c6326b4ed44adad9ec93fff63272a DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Daria Di Molfetta verfasserin aut ECM Composition Differentially Regulates Intracellular and Extracellular pH in Normal and Cancer Pancreatic Duct Epithelial Cells 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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<sup<+</sup</H<sup<+</sup< 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<sub<3</sub< 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<sub<3</sub<, especially in HPDE cells on a normal ECM; (iii) cancer cell NHE1 activity is less affected by NaHCO<sub<3</sub<. We conclude that ECM composition and the fluctuations of pHe cooperate to predispose pHi homeostasis towards the presence of NaHCO<sub<3</sub< gradients similar to that expected in the tumor. PDAC NHE1 bicarbonate transport Biology (General) Chemistry Stefania Cannone verfasserin aut Maria Raffaella Greco verfasserin aut Rosa Caroppo verfasserin aut Francesca Piccapane verfasserin aut Tiago Miguel Amaral Carvalho verfasserin aut Concetta Altamura verfasserin aut Ilaria Saltarella verfasserin aut Diana Tavares Valente verfasserin aut Jean Francois Desaphy verfasserin aut Stephan J. Reshkin verfasserin aut Rosa Angela Cardone verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 24(2023), 13, p 10632 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:24 year:2023 number:13, p 10632 https://doi.org/10.3390/ijms241310632 kostenfrei https://doaj.org/article/b90c6326b4ed44adad9ec93fff63272a kostenfrei https://www.mdpi.com/1422-0067/24/13/10632 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 24 2023 13, p 10632
allfieldsGer	10.3390/ijms241310632 doi (DE-627)DOAJ094011702 (DE-599)DOAJb90c6326b4ed44adad9ec93fff63272a DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Daria Di Molfetta verfasserin aut ECM Composition Differentially Regulates Intracellular and Extracellular pH in Normal and Cancer Pancreatic Duct Epithelial Cells 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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<sup<+</sup</H<sup<+</sup< 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<sub<3</sub< 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<sub<3</sub<, especially in HPDE cells on a normal ECM; (iii) cancer cell NHE1 activity is less affected by NaHCO<sub<3</sub<. We conclude that ECM composition and the fluctuations of pHe cooperate to predispose pHi homeostasis towards the presence of NaHCO<sub<3</sub< gradients similar to that expected in the tumor. PDAC NHE1 bicarbonate transport Biology (General) Chemistry Stefania Cannone verfasserin aut Maria Raffaella Greco verfasserin aut Rosa Caroppo verfasserin aut Francesca Piccapane verfasserin aut Tiago Miguel Amaral Carvalho verfasserin aut Concetta Altamura verfasserin aut Ilaria Saltarella verfasserin aut Diana Tavares Valente verfasserin aut Jean Francois Desaphy verfasserin aut Stephan J. Reshkin verfasserin aut Rosa Angela Cardone verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 24(2023), 13, p 10632 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:24 year:2023 number:13, p 10632 https://doi.org/10.3390/ijms241310632 kostenfrei https://doaj.org/article/b90c6326b4ed44adad9ec93fff63272a kostenfrei https://www.mdpi.com/1422-0067/24/13/10632 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 24 2023 13, p 10632
allfieldsSound	10.3390/ijms241310632 doi (DE-627)DOAJ094011702 (DE-599)DOAJb90c6326b4ed44adad9ec93fff63272a DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Daria Di Molfetta verfasserin aut ECM Composition Differentially Regulates Intracellular and Extracellular pH in Normal and Cancer Pancreatic Duct Epithelial Cells 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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<sup<+</sup</H<sup<+</sup< 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<sub<3</sub< 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<sub<3</sub<, especially in HPDE cells on a normal ECM; (iii) cancer cell NHE1 activity is less affected by NaHCO<sub<3</sub<. We conclude that ECM composition and the fluctuations of pHe cooperate to predispose pHi homeostasis towards the presence of NaHCO<sub<3</sub< gradients similar to that expected in the tumor. PDAC NHE1 bicarbonate transport Biology (General) Chemistry Stefania Cannone verfasserin aut Maria Raffaella Greco verfasserin aut Rosa Caroppo verfasserin aut Francesca Piccapane verfasserin aut Tiago Miguel Amaral Carvalho verfasserin aut Concetta Altamura verfasserin aut Ilaria Saltarella verfasserin aut Diana Tavares Valente verfasserin aut Jean Francois Desaphy verfasserin aut Stephan J. Reshkin verfasserin aut Rosa Angela Cardone verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 24(2023), 13, p 10632 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:24 year:2023 number:13, p 10632 https://doi.org/10.3390/ijms241310632 kostenfrei https://doaj.org/article/b90c6326b4ed44adad9ec93fff63272a kostenfrei https://www.mdpi.com/1422-0067/24/13/10632 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 24 2023 13, p 10632
language	English
source	In International Journal of Molecular Sciences 24(2023), 13, p 10632 volume:24 year:2023 number:13, p 10632
sourceStr	In International Journal of Molecular Sciences 24(2023), 13, p 10632 volume:24 year:2023 number:13, p 10632
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	PDAC NHE1 bicarbonate transport Biology (General) Chemistry
isfreeaccess_bool	true
container_title	International Journal of Molecular Sciences
authorswithroles_txt_mv	Daria Di Molfetta @@aut@@ Stefania Cannone @@aut@@ Maria Raffaella Greco @@aut@@ Rosa Caroppo @@aut@@ Francesca Piccapane @@aut@@ Tiago Miguel Amaral Carvalho @@aut@@ Concetta Altamura @@aut@@ Ilaria Saltarella @@aut@@ Diana Tavares Valente @@aut@@ Jean Francois Desaphy @@aut@@ Stephan J. Reshkin @@aut@@ Rosa Angela Cardone @@aut@@
publishDateDaySort_date	2023-01-01T00:00:00Z
hierarchy_top_id	316340715
id	DOAJ094011702
language_de	englisch
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callnumber-first	Q - Science
author	Daria Di Molfetta
spellingShingle	Daria Di Molfetta misc QH301-705.5 misc QD1-999 misc PDAC misc NHE1 misc bicarbonate transport misc Biology (General) misc Chemistry ECM Composition Differentially Regulates Intracellular and Extracellular pH in Normal and Cancer Pancreatic Duct Epithelial Cells
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topic_title	QH301-705.5 QD1-999 ECM Composition Differentially Regulates Intracellular and Extracellular pH in Normal and Cancer Pancreatic Duct Epithelial Cells PDAC NHE1 bicarbonate transport
topic	misc QH301-705.5 misc QD1-999 misc PDAC misc NHE1 misc bicarbonate transport misc Biology (General) misc Chemistry
topic_unstemmed	misc QH301-705.5 misc QD1-999 misc PDAC misc NHE1 misc bicarbonate transport misc Biology (General) misc Chemistry
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title	ECM Composition Differentially Regulates Intracellular and Extracellular pH in Normal and Cancer Pancreatic Duct Epithelial Cells
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title_full	ECM Composition Differentially Regulates Intracellular and Extracellular pH in Normal and Cancer Pancreatic Duct Epithelial Cells
author_sort	Daria Di Molfetta
journal	International Journal of Molecular Sciences
journalStr	International Journal of Molecular Sciences
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author_browse	Daria Di Molfetta Stefania Cannone Maria Raffaella Greco Rosa Caroppo Francesca Piccapane Tiago Miguel Amaral Carvalho Concetta Altamura Ilaria Saltarella Diana Tavares Valente Jean Francois Desaphy Stephan J. Reshkin Rosa Angela Cardone
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author-letter	Daria Di Molfetta
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author2-role	verfasserin
title_sort	ecm composition differentially regulates intracellular and extracellular ph in normal and cancer pancreatic duct epithelial cells
callnumber	QH301-705.5
title_auth	ECM Composition Differentially Regulates Intracellular and Extracellular pH in Normal and Cancer Pancreatic Duct Epithelial Cells
abstract	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<sup<+</sup</H<sup<+</sup< 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<sub<3</sub< 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<sub<3</sub<, especially in HPDE cells on a normal ECM; (iii) cancer cell NHE1 activity is less affected by NaHCO<sub<3</sub<. We conclude that ECM composition and the fluctuations of pHe cooperate to predispose pHi homeostasis towards the presence of NaHCO<sub<3</sub< gradients similar to that expected in the tumor.
abstractGer	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<sup<+</sup</H<sup<+</sup< 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<sub<3</sub< 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<sub<3</sub<, especially in HPDE cells on a normal ECM; (iii) cancer cell NHE1 activity is less affected by NaHCO<sub<3</sub<. We conclude that ECM composition and the fluctuations of pHe cooperate to predispose pHi homeostasis towards the presence of NaHCO<sub<3</sub< gradients similar to that expected in the tumor.
abstract_unstemmed	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<sup<+</sup</H<sup<+</sup< 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<sub<3</sub< 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<sub<3</sub<, especially in HPDE cells on a normal ECM; (iii) cancer cell NHE1 activity is less affected by NaHCO<sub<3</sub<. We conclude that ECM composition and the fluctuations of pHe cooperate to predispose pHi homeostasis towards the presence of NaHCO<sub<3</sub< gradients similar to that expected in the tumor.
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title_short	ECM Composition Differentially Regulates Intracellular and Extracellular pH in Normal and Cancer Pancreatic Duct Epithelial Cells
url	https://doi.org/10.3390/ijms241310632 https://doaj.org/article/b90c6326b4ed44adad9ec93fff63272a https://www.mdpi.com/1422-0067/24/13/10632 https://doaj.org/toc/1661-6596 https://doaj.org/toc/1422-0067
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