Aquaporin-3 and Aquaporin-5 Facilitate Migration and Cell-Cell Adhesion in Pancreatic Cancer by Modulating Cell Biomechanical Properties.

aquaglyceroporins aquaporins atomic force microscopy cell–cell adhesion hydrogen peroxide membrane fluidity pancreatic cancer

Journal

Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052

Informations de publication

Date de publication:
12 04 2022
Historique:
received: 11 02 2022
revised: 05 04 2022
accepted: 08 04 2022
entrez: 23 4 2022
pubmed: 24 4 2022
medline: 27 4 2022
Statut: epublish

Résumé

Aquaporins are membrane channels responsible for the bidirectional transfer of water and small non-charged solutes across cell membranes. AQP3 and AQP5 are overexpressed in pancreatic ductal adenocarcinoma, playing key roles in cell migration, proliferation, and invasion. Here, we evaluated AQP3 and AQP5 involvement in cell biomechanical properties, cell-cell adhesion, and cell migration, following a loss-of-function strategy on BxPC-3 cells. Silencing of AQP3 and AQP5 was functionally validated by reduced membrane permeability and had implications on cell migration, slowing wound recovery. Moreover, silenced AQP5 and AQP3/5 cells showed higher membrane fluidity. Biomechanical and morphological changes were assessed by atomic force microscopy (AFM), revealing AQP5 and AQP3/5 silenced cells with a lower stiffness than their control. Through cell-cell adhesion measurements, the work (energy) necessary to detach two cells was found to be lower for AQP-silenced cells than control, showing that these AQPs have implications on cell-cell adhesion. These findings highlight AQP3 and AQP5 involvement in the biophysical properties of cell membranes, whole cell biomechanical properties, and cell-cell adhesion, thus having potential implication in the settings of tumor development.

Sections du résumé

BACKGROUND
Aquaporins are membrane channels responsible for the bidirectional transfer of water and small non-charged solutes across cell membranes. AQP3 and AQP5 are overexpressed in pancreatic ductal adenocarcinoma, playing key roles in cell migration, proliferation, and invasion. Here, we evaluated AQP3 and AQP5 involvement in cell biomechanical properties, cell-cell adhesion, and cell migration, following a loss-of-function strategy on BxPC-3 cells.
RESULTS
Silencing of AQP3 and AQP5 was functionally validated by reduced membrane permeability and had implications on cell migration, slowing wound recovery. Moreover, silenced AQP5 and AQP3/5 cells showed higher membrane fluidity. Biomechanical and morphological changes were assessed by atomic force microscopy (AFM), revealing AQP5 and AQP3/5 silenced cells with a lower stiffness than their control. Through cell-cell adhesion measurements, the work (energy) necessary to detach two cells was found to be lower for AQP-silenced cells than control, showing that these AQPs have implications on cell-cell adhesion.
CONCLUSION
These findings highlight AQP3 and AQP5 involvement in the biophysical properties of cell membranes, whole cell biomechanical properties, and cell-cell adhesion, thus having potential implication in the settings of tumor development.

Identifiants

pubmed: 35455986
pii: cells11081308
doi: 10.3390/cells11081308
pmc: PMC9030499
pii:
doi:

Substances chimiques

AQP3 protein, human 0
AQP5 protein, human 0
Aquaporin 5 0
Aquaporin 3 158801-98-0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

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Auteurs

Patrícia M Silva (PM)

Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal.

Inês V da Silva (IV)

Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal.
Department of Pharmaceutical Sciences and Medicines, Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal.

Maria J Sarmento (MJ)

Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal.

Ítala C Silva (ÍC)

Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal.

Filomena A Carvalho (FA)

Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal.

Graça Soveral (G)

Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal.
Department of Pharmaceutical Sciences and Medicines, Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal.

Nuno C Santos (NC)

Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal.

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Classifications MeSH