Differential expression of aquaporin‐3 and aquaporin‐5 in pancreatic ductal adenocarcinoma

Direito, Inês; Paulino, Jorge; Vigia, Emanuel; Brito, Maria Alexandra; Soveral, Graça

doi:10.1002/jso.24605

Cited by 47 publications

(54 citation statements)

References 50 publications

(151 reference statements)

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“…AQP1 and AQP5 are increasingly expressed at the apical membrane of intercalated pancreatic duct cells [226], and increased AQP5 levels result into "retinoblastoma protein phosphorylation through the formation of a nuclear complex with cyclin D1 and CDK4" [227]. AQP3 was found to be increased in advanced stages of pancreatic cancer, and AQP5 is more closely associated with tumor differentiation [228].…”

Section: Aquaporines (Apq)mentioning

confidence: 99%

Chronic inflammation evoked by pathogenic stimulus during carcinogenesis

Brücher

Jamall

2019

4open

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A pathogenic (biological or chemical) stimulus is the earliest information received by a cell that can result in the disruption of homeostasis with consequent development of disease. Chronic inflammation involves many cell types with numerous cytokines and signaling pathways, the release of different components by the cells, and the crosstalk provoked by such stimuli involving subclinical chronic inflammation and is mechanistically manifold. Exosomes secrete chemicals that trigger the epithelium to produce exosome-like nanoparticles promoting chronic inflammation. Small molecules, together with various cytokines, selectively target signaling pathways inducing crosstalk that suppress apoptosis. 16S rRNA gene sequencing has become routine to provide information on the composition and abundance of bacteria found in human tissues and in reservoirs. The deregulation of autophagy with chronic stimulation of inflammation is an early phenomenon in carcinogenesis. The disruption of cell–cell integrity enables transcellular CagA migration and triggers deregulation of autophagy with the net result being chronic inflammation. The complex and insidious nature of chronic inflammation can be seen both inside and outside the cell and even with intracellular nuclear fragments such as chromatin, which itself can elicit a chronic inflammatory response within the cytoplasm and affect autophagy. The ultimate result of unresolved chronic inflammation is fibrosis, a step before tissue remodeling results in the formation of a precancerous niche (PCN). Various pathogenic stimuli associated with different neoplasms result in persistent inflammation. This ongoing disruption of homeostasis in the micromilieu of cells, tissues, and organs is an essential preamble to carcinogenesis and occurs early in that process.

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Section: Aquaporines (Apq)mentioning

confidence: 99%

Chronic inflammation evoked by pathogenic stimulus during carcinogenesis

Brücher

Jamall

2019

4open

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“…Several studies described the aberrant expression of aquaporins (AQPs) in different human cancer cells and tissues, frequently correlated with tumor stage and aggressiveness [14,15]. AQPs are highly conserved transmembrane proteins that facilitate the diffusion of water and glycerol across cell membranes, crucial for water and energy homeostasis [16].…”

Section: Introductionmentioning

confidence: 99%

The Aquaporin-3-Inhibiting Potential of Polyoxotungstates

Pimpão

Silva

Mósca

et al. 2020

IJMS

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Polyoxometalates (POMs) are of increasing interest due to their proven anticancer activities. Aquaporins (AQPs) were found to be overexpressed in tumors bringing particular attention to their inhibitors as anticancer drugs. Herein, we report for the first time the ability of polyoxotungstates (POTs), such as of Wells–Dawson P2W18, P2W12, and P2W15, and Preyssler P5W30 structures, to affect aquaporin-3 (AQP3) activity and impair melanoma cell migration. The tested POTs were revealed to inhibit AQP3 function with different effects, with P2W18, P2W12, and P5W30 being the most potent (50% inhibitory concentration (IC50) = 0.8, 2.8, and 3.2 µM), and P2W15 being the weakest (IC50 > 100 µM). The selectivity of P2W18 toward AQP3 was confirmed in yeast cells transformed with human aquaglyceroporins. The effect of P2W12 and P2W18 on melanoma cells that highly express AQP3 revealed an impairment of cell migration between 55% and 65% after 24 h, indicating that the anticancer properties of these compounds may in part be due to the blockage of AQP3-mediated permeability. Altogether, our data revealed that P2W18 strongly affects AQP3 activity and cancer cell growth, unveiling its potential as an anticancer drug against tumors where AQP3 is highly expressed.

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“…Development of gastric adenocarcinomas is a stepwise progression of histologic lesions, starting with gastritis, followed by intestinal metaplasia, dysplasia, and eventually invasive adenocarcinoma. AQP3 has been reported to associate with human cancer progression and metastasis, such as pancreatic ductal adenocarcinoma, prostate cancer, cervical intraepithelial neoplasia, and triple-negative breast cancer [22][23][24][25][26]. However, the role of AQP3 and its expression pattern in gastric carcinogenesis remain unclear.…”

Section: Discussionmentioning

confidence: 99%

Aquaporin 3 Expression Pattern in Gastric Diseases and its significance

Dai²,

Dou

et al. 2020

Preprint

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Background Aquaporin 3(AQP3) has been implicated in gastric intestinal metaplasia and gastric cancer, and considered as a biomarker to improve treatment strategy. Accumulating evidence suggests that AQP3 is involved in the gastric carcinogenesis and the disease progression. However, whether AQP3 is involved in the transformation from gastritis to gastric cancer remain elusive. In this study, we intended to realized the expression pattern and its significance of AQP3 in different gastric diseases. Methods A total of 101 patients diagnosed with gastric diseases were included in the study. A gastric tissue biopsy was taken from the gastric antrum during endoscopic examination. Expression of AQP3 protein is determined by immunohistochemistry using polyclonal rabbit anti-AQP3 antibody. Percentage of positive cells and staining intensity were counted and measured. Results The frequency of AQP3 positivity was similar between the disease types of chronic gastritis, gastric ulcer, gastric erosion, and atrophic gastritis, whereas the frequency of AQP3 positivity was significantly higher in patients with gastric intestinal metaplasia、gastric dysplasia 、gastric polyps and intestinal-type gastric adenocarcinoma than that in patients with gastritis, gastric ulcer, gastric erosion, or atrophic gastritis(p<0.0001, p=0.001, p=0.006, p=0.0009, respectively), especially in the patients with hyperplastic polyps (p<0.0001). Conclusion The frequency of AQP3 positivity was significantly higher in patients with gastric intestinal metaplasia, gastric dysplasia, and gastric adenocarcinoma, and the frequency between them was similar, suggesting that AQP3 expression is peaked at the stage of gastric intestinal metaplasia, which further confirmed that gastric intestinal metaplasia is a pivotal progression in gastric carcinogenesis pathologically. Interestingly, it is the first time to report AQP3 positive expression in patients with gastric polyps. In short, AQP3 is involved in the progression from gastritis to gastric adenocarcinoma, and might be a potential biomarker to improve the treatment strategy of gastric cancer.

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Differential expression of aquaporin‐3 and aquaporin‐5 in pancreatic ductal adenocarcinoma

Abstract: These findings suggest AQP3 and AQP5 involvement in PDA development and the usefulness of AQP5 in early PDA diagnosis.

Cited by 47 publications

References 50 publications

Chronic inflammation evoked by pathogenic stimulus during carcinogenesis

Chronic inflammation evoked by pathogenic stimulus during carcinogenesis

The Aquaporin-3-Inhibiting Potential of Polyoxotungstates

Aquaporin 3 Expression Pattern in Gastric Diseases and its significance

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