{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T12:24:27Z","timestamp":1782822267235,"version":"3.54.5"},"reference-count":124,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T00:00:00Z","timestamp":1772150400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T00:00:00Z","timestamp":1772150400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["GRK 2515 (Chembion)"],"award-info":[{"award-number":["GRK 2515 (Chembion)"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["PE 3917\/2\u20101"],"award-info":[{"award-number":["PE 3917\/2\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Physiologica"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>Pancreatic ductal adenocarcinoma (PDAC) develops within a uniquely dynamic pH landscape shaped by substantial acid\u2013base fluxes produced by the exocrine pancreas. Secretion of alkaline pancreatic juice, normally linked to digestion, produces intermittent acidifications of the pancreatic interstitium, which challenges epithelial and stromal cells. It was postulated that these unique pancreatic pH dynamics can facilitate PDAC initiation and progression through selection of a more aggressive phenotype emerging with PDAC driver mutations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Here, we summarize evidence that pH\u2010regulatory transport proteins have an important role in shaping the PDAC microenvironment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>pH\u2010regulatory transport proteins generate and sense their microenvironment and act as signaling hubs to regulate proliferation, migration, and metabolism, and immune evasion. In this way, transport proteins that are crucial for the normal physiology of the exocrine pancreas are misused and become coerced into playing a pro\u2010cancer role in pancreatic tumor cells, pancreatic stellate cells, or infiltrating immune cells. Experiments with PDAC mouse models revealed a therapeutic potential of targeting pH dynamics, notably by inhibition or genetic ablation of pH\u2010regulatory proteins. It is a consistent finding that these maneuvers have a marked impact on the tumor immune defense and the communication between cancer and immune cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Collectively, we present a case for considering pH\u2010regulating proteins as a therapeutic avenue.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/apha.70183","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T11:50:45Z","timestamp":1772970645000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<scp>pH<\/scp>\n                    \u2010Dependent Microenvironmental Ionic Signaling in Pancreatic Ductal Adenocarcinoma"],"prefix":"10.1111","volume":"242","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9280-2099","authenticated-orcid":false,"given":"Albrecht","family":"Schwab","sequence":"first","affiliation":[{"name":"Institut f\u00fcr Physiologie II University of M\u00fcnster  M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micol","family":"Rugi","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Physiologie II University of M\u00fcnster  M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pawel","family":"Swietach","sequence":"additional","affiliation":[{"name":"Department of Physiology, Anatomy and Genetics University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wiktoria","family":"B\u0142aszczak","sequence":"additional","affiliation":[{"name":"Department of Physiology, Anatomy and Genetics University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivana","family":"Novak","sequence":"additional","affiliation":[{"name":"Section for Cell Biology and Physiology Department of Biology University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ganga","family":"Deshar","sequence":"additional","affiliation":[{"name":"Section for Cell Biology and Physiology Department of Biology University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stine Falsig","family":"Pedersen","sequence":"additional","affiliation":[{"name":"Section for Cell Biology and Physiology Department of Biology University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata","family":"Ialchina","sequence":"additional","affiliation":[{"name":"Section for Cell Biology and Physiology Department of Biology University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albin","family":"Sandelin","sequence":"additional","affiliation":[{"name":"The Bioinformatics Center, Department of Biology University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayi","family":"Yao","sequence":"additional","affiliation":[{"name":"The Bioinformatics Center, Department of Biology University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan J.","family":"Reshkin","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Biotechnology and Environment University of Bari  Bari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2011-9135","authenticated-orcid":false,"given":"Rosa A.","family":"Cardone","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Biotechnology and Environment University of Bari  Bari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiago M. 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