{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T18:03:11Z","timestamp":1772733791829,"version":"3.50.1"},"reference-count":55,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2023,8,31]],"date-time":"2023-08-31T00:00:00Z","timestamp":1693440000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Aquaporins are water channels that facilitate passive water transport across cellular membranes following an osmotic gradient and are essential in the regulation of body water homeostasis. Several aquaporins are overexpressed in breast cancer, and AQP1, AQP3 and AQP5 have been linked to spread to lymph nodes and poor prognosis. The subgroup aquaglyceroporins also facilitate the transport of glycerol and are thus involved in cellular metabolism. Transcriptomic analysis revealed that the three aquaglyceroporins, AQP3, AQP7 and AQP9, but not AQP10, are overexpressed in human breast cancer. It is, however, unknown if they are all expressed in the same cells or have a heterogeneous expression pattern. To investigate this, we employed immunohistochemical analysis of serial sections from human invasive ductal and lobular breast cancers. We found that AQP3, AQP7 and AQP9 are homogeneously expressed in almost all cells in both premalignant in situ lesions and invasive lesions. Thus, potential intervention strategies targeting cellular metabolism via the aquaglyceroporins should consider all three expressed aquaglyceroporins, namely AQP3, AQP7 and AQP9.<\/jats:p>","DOI":"10.3390\/cells12172185","type":"journal-article","created":{"date-parts":[[2023,8,31]],"date-time":"2023-08-31T09:42:53Z","timestamp":1693474973000},"page":"2185","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Aquaglyceroporins in Human Breast Cancer"],"prefix":"10.3390","volume":"12","author":[{"given":"Teresa","family":"Kirkegaard","sequence":"first","affiliation":[{"name":"Department of Clinical Medicine, Aarhus University, 8200 Aarhus N, Denmark"},{"name":"Department of Molecular Biology and Genetics, Aarhus University, 8000 Aarhus C, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-4486-5994","authenticated-orcid":false,"given":"Andreas","family":"Riishede","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Aarhus University, 8200 Aarhus N, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Trine","family":"Tramm","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Aarhus University, 8200 Aarhus N, Denmark"},{"name":"Department of Pathology, Aarhus University Hospital, 8200 Aarhus N, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4368-8821","authenticated-orcid":false,"given":"Lene N.","family":"Nejsum","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Aarhus University, 8200 Aarhus N, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1038\/s41581-023-00734-9","article-title":"Aquaporin water channels: Roles beyond renal water handling","volume":"19","author":"Login","year":"2023","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1550","DOI":"10.1016\/j.scib.2020.12.006","article-title":"The structural basis for glycerol permeation by human AQP7","volume":"66","author":"Zhang","year":"2021","journal-title":"Sci. Bull."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"4749","DOI":"10.1038\/s41467-018-07176-z","article-title":"Human adipose glycerol flux is regulated by a pH gate in AQP10","volume":"9","author":"Gotfryd","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"eaay2176","DOI":"10.1126\/scitranslmed.aay2176","article-title":"Inhibition of aquaporin-1 prevents myocardial remodeling by blocking the transmembrane transport of hydrogen peroxide","volume":"12","author":"Montiel","year":"2020","journal-title":"Sci. Transl. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"183065","DOI":"10.1016\/j.bbamem.2019.183065","article-title":"Characterization of aquaporin-driven hydrogen peroxide transport","volume":"1862","author":"Wang","year":"2020","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"15681","DOI":"10.1073\/pnas.1005776107","article-title":"Aquaporin-3 mediates hydrogen peroxide uptake to regulate downstream intracellular signaling","volume":"107","author":"Miller","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Rodrigues, C., Pimpao, C., Mosca, A.F., Coxixo, A.S., Lopes, D., da Silva, I.V., Pedersen, P.A., Antunes, F., and Soveral, G. (2019). Human Aquaporin-5 Facilitates Hydrogen Peroxide Permeation Affecting Adaption to Oxidative Stress and Cancer Cell Migration. Cancers, 11.","DOI":"10.3390\/cancers11070932"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Pellavio, G., Martinotti, S., Patrone, M., Ranzato, E., and Laforenza, U. (2022). Aquaporin-6 May Increase the Resistance to Oxidative Stress of Malignant Pleural Mesothelioma Cells. Cells, 11.","DOI":"10.3390\/cells11121892"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1074\/jbc.M603761200","article-title":"Specific aquaporins facilitate the diffusion of hydrogen peroxide across membranes","volume":"282","author":"Bienert","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.1089\/ars.2013.5330","article-title":"Tyrosine kinase signal modulation: A matter of H2O2 membrane permeability?","volume":"19","author":"Bertolotti","year":"2013","journal-title":"Antioxid. Redox Signal."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.bbrc.2016.01.153","article-title":"Aquaporin-9 facilitates membrane transport of hydrogen peroxide in mammalian cells","volume":"471","author":"Watanabe","year":"2016","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"101326","DOI":"10.1016\/j.redox.2019.101326","article-title":"Human aquaporin-11 guarantees efficient transport of H2O2 across the endoplasmic reticulum membrane","volume":"28","author":"Bestetti","year":"2020","journal-title":"Redox Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"4071","DOI":"10.1158\/0008-5472.CAN-19-2269","article-title":"Aquaporin-7 Regulates the Response to Cellular Stress in Breast Cancer","volume":"80","author":"Dai","year":"2020","journal-title":"Cancer Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1126\/science.8140421","article-title":"Requirement of human renal water channel aquaporin-2 for vasopressin-dependent concentration of urine","volume":"264","author":"Deen","year":"1994","journal-title":"Science"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5450","DOI":"10.1073\/pnas.94.10.5450","article-title":"Congestive heart failure in rats is associated with increased expression and targeting of aquaporin-2 water channel in collecting duct","volume":"94","author":"Nielsen","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1500","DOI":"10.1172\/JCI119312","article-title":"Upregulation of aquaporin-2 water channel expression in chronic heart failure rat","volume":"99","author":"Xu","year":"1997","journal-title":"J. Clin. Investig."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1838","DOI":"10.1172\/JCI117863","article-title":"Lithium-induced downregulation of aquaporin-2 water channel expression in rat kidney medulla","volume":"95","author":"Marples","year":"1995","journal-title":"J. Clin. Investig."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/apm.13192","article-title":"Aquaporin-1 in breast cancer","volume":"130","author":"Login","year":"2022","journal-title":"APMIS"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1111\/apm.13212","article-title":"Aquaporin-5 in breast cancer","volume":"130","author":"Bystrup","year":"2022","journal-title":"APMIS"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1111\/apm.13184","article-title":"Aquaporins in pancreatic ductal adenocarcinoma","volume":"129","author":"Edamana","year":"2021","journal-title":"APMIS"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Tomita, Y., Dorward, H., Yool, A.J., Smith, E., Townsend, A.R., Price, T.J., and Hardingham, J.E. (2017). Role of Aquaporin 1 Signalling in Cancer Development and Progression. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18020299"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Marlar, S., Jensen, H.H., Login, F.H., and Nejsum, L.N. (2017). Aquaporin-3 in Cancer. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18102106"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.biocel.2016.09.005","article-title":"The role of aquaporin-5 in cancer cell migration: A potential active participant","volume":"79","author":"Jensen","year":"2016","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1128\/MCB.01482-07","article-title":"Prevention of skin tumorigenesis and impairment of epidermal cell proliferation by targeted aquaporin-3 gene disruption","volume":"28","author":"Verkman","year":"2008","journal-title":"Mol. Cell. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"6026","DOI":"10.1128\/MCB.00384-07","article-title":"Aquaporin 7 is a beta-cell protein and regulator of intraislet glycerol content and glycerol kinase activity, beta-cell mass, and insulin production and secretion","volume":"27","author":"Matsumura","year":"2007","journal-title":"Mol. Cell. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"6980","DOI":"10.1096\/fj.201802068RR","article-title":"Aquaporins differentially regulate cell-cell adhesion in MDCK cells","volume":"33","author":"Login","year":"2019","journal-title":"FASEB J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1038\/s41467-023-36272-y","article-title":"Cryo-EM structure supports a role of AQP7 as a junction protein","volume":"14","author":"Huang","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"C771","DOI":"10.1152\/ajpcell.00608.2020","article-title":"Aquaporin water channels as regulators of cell-cell adhesion proteins","volume":"320","author":"Edamana","year":"2021","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1007\/s00424-007-0357-5","article-title":"Aquaporins and cell migration","volume":"456","author":"Papadopoulos","year":"2008","journal-title":"Pflugers Arch."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"C208","DOI":"10.1152\/ajpcell.00502.2022","article-title":"The multifaceted role of aquaporins in physiological cell migration","volume":"325","author":"Smith","year":"2023","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Jung, H.J., Park, J.Y., Jeon, H.S., and Kwon, T.H. (2011). Aquaporin-5: A marker protein for proliferation and migration of human breast cancer cells. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0028492"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"C307","DOI":"10.1152\/ajpcell.00311.2022","article-title":"The cell polarity protein Scribble is downregulated by the water channel aquaporin-5 in breast cancer cells","volume":"324","author":"Edamana","year":"2023","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3904","DOI":"10.1002\/cam4.3032","article-title":"Aquaporin 1 elicits cell motility and coordinates vascular bed formation by downregulating thrombospondin type-1 domain-containing 7A in glioblastoma","volume":"9","author":"Oishi","year":"2020","journal-title":"Cancer Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1002\/glia.20524","article-title":"Expression and function of water channels (aquaporins) in migrating malignant astrocytes","volume":"55","author":"McCoy","year":"2007","journal-title":"Glia"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1186\/1756-9966-30-86","article-title":"Aquaporin-3 positively regulates matrix metalloproteinases via PI3K\/AKT signal pathway in human gastric carcinoma SGC7901 cells","volume":"30","author":"Xu","year":"2011","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Roche, J.V., and Tornroth-Horsefield, S. (2017). Aquaporin Protein-Protein Interactions. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18112255"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"C282","DOI":"10.1152\/ajpcell.00496.2020","article-title":"Aquaporin-5 regulation of cell-cell adhesion proteins: An elusive \u201ctail\u201d story","volume":"320","author":"Login","year":"2021","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1708","DOI":"10.1016\/j.cell.2023.01.040","article-title":"Deciphering breast cancer: From biology to the clinic","volume":"186","author":"Nolan","year":"2023","journal-title":"Cell"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"23","DOI":"10.4137\/CPath.S31563","article-title":"Diversity of Breast Carcinoma: Histological Subtypes and Clinical Relevance","volume":"8","author":"Makki","year":"2015","journal-title":"Clin. Med. Insights Pathol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Chow, P.H., Bowen, J., and Yool, A.J. (2020). Combined Systematic Review and Transcriptomic Analyses of Mammalian Aquaporin Classes 1 to 10 as Biomarkers and Prognostic Indicators in Diverse Cancers. Cancers, 12.","DOI":"10.3390\/cancers12071911"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1245\/s10434-013-3317-7","article-title":"AQP5 expression predicts survival in patients with early breast cancer","volume":"21","author":"Lee","year":"2014","journal-title":"Ann. Surg. Oncol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"8143","DOI":"10.18632\/oncotarget.6994","article-title":"Expression of aquaporin1, a water channel protein, in cytoplasm is negatively correlated with prognosis of breast cancer patients","volume":"7","author":"Qin","year":"2016","journal-title":"Oncotarget"},{"key":"ref_44","first-page":"2661","article-title":"Expression of AQP3 and AQP5 as a prognostic marker in triple-negative breast cancer","volume":"16","author":"Zhu","year":"2018","journal-title":"Oncol. Lett."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.2147\/CMAR.S193396","article-title":"Significant prognostic values of aquaporin mRNA expression in breast cancer","volume":"11","author":"Zhu","year":"2019","journal-title":"Cancer Manag. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1016\/j.bbrc.2017.09.125","article-title":"Immunohistochemical evalulation of activated Ras and Rac1 as potential downstream effectors of aquaporin-5 in breast cancer in vivo","volume":"493","author":"Jensen","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"S215","DOI":"10.1007\/s00592-012-0430-1","article-title":"Gender-specific effect of physical training on AQP7 protein expression in human adipose tissue","volume":"49","author":"Lebeck","year":"2012","journal-title":"Acta Diabetol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1369\/0022155416641028","article-title":"A Systematic Characterization of Aquaporin-9 Expression in Human Normal and Pathological Tissues","volume":"64","author":"Lindskog","year":"2016","journal-title":"J. Histochem. Cytochem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1006\/bbrc.2000.3505","article-title":"Immunolocalization of AQP9 in liver, epididymis, testis, spleen, and brain","volume":"276","author":"Elkjaer","year":"2000","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"16878","DOI":"10.1038\/s41598-017-17204-5","article-title":"QuPath: Open source software for digital pathology image analysis","volume":"7","author":"Bankhead","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3786","DOI":"10.1172\/JCI60534","article-title":"Heterogeneity in breast cancer","volume":"121","author":"Polyak","year":"2011","journal-title":"J. Clin. Investig."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s10735-004-2633-4","article-title":"Distribution of AQP2 and AQP3 water channels in human tissue microarrays","volume":"36","author":"Mobasheri","year":"2005","journal-title":"J. Mol. Histol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2882","DOI":"10.3892\/mmr.2014.3097","article-title":"Aquaporin 3 promotes prostate cancer cell motility and invasion via extracellular signal-regulated kinase 1\/2-mediated matrix metalloproteinase-3 secretion","volume":"11","author":"Chen","year":"2015","journal-title":"Mol. Med. Rep."},{"key":"ref_54","first-page":"1548","article-title":"Downregulation of aquaporin 9 decreases catabolic factor expression through nuclear factor-kappaB signaling in chondrocytes","volume":"42","author":"Takeuchi","year":"2018","journal-title":"Int. J. Mol. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.bbrc.2022.11.096","article-title":"Aquaporin water channels affect the response of conventional anticancer therapies of 3D grown breast cancer cells","volume":"639","author":"Edamana","year":"2023","journal-title":"Biochem. Biophys. Res. Commun."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/17\/2185\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:43:39Z","timestamp":1760129019000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/17\/2185"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,31]]},"references-count":55,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2023,9]]}},"alternative-id":["cells12172185"],"URL":"https:\/\/doi.org\/10.3390\/cells12172185","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,31]]}}}