Expression of aquaporin-1 is a poor prognostic factor for stage II and III colon cancer

Yoshida, Toru; Hojo, Satoru; Sekine, Satoshi; Sawada, Shigeaki; Okumura, Tomoyuki; Nagata, Takuya; Shimada, Yutaka; Tsukada, Kazuhiro

doi:10.3892/mco.2013.165

Cited by 58 publications

(56 citation statements)

References 18 publications

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“…Although the precise mechanism for AQP1-enhanced motility remains unknown, both ion and water channels are essential in the cellular migration process (Schwab et al, 2007). AQP1 expression has been linked to metastasis and invasiveness of colon cancer cells (Jiang, 2009;Yoshida et al, 2013). In mammary and melanoma cancer cells, AQP1 facilitates tumor cell migration in vitro and metastasis in vivo (Hu and Verkman, 2006).…”

Section: Introductionmentioning

confidence: 99%

Bumetanide Derivatives AqB007 and AqB011 Selectively Block the Aquaporin-1 Ion Channel Conductance and Slow Cancer Cell Migration

et al. 2015

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Aquaporins (AQPs) in the major intrinsic family of proteins mediate fluxes of water and other small solutes across cell membranes. AQP1 is a water channel, and under permissive conditions, a nonselective cation channel gated by cGMP. In addition to mediating fluid transport, AQP1 expression facilitates rapid cell migration in cell types including colon cancers and glioblastoma. Work here defines new pharmacological derivatives of bumetanide that selectively inhibit the ion channel, but not the water channel, activity of AQP1. Human AQP1 was analyzed in the Xenopus laevis oocyte expression system by two-electrode voltage clamp and optical osmotic swelling assays. The aquaporin ligand bumetanide derivative AqB011 was the most potent blocker of the AQP1 ion conductance (IC 50 of 14 mM), with no effect on water channel activity (at up to 200 mM). The order of potency for inhibition of the ionic conductance was AqB011 . AqB007 .. AqB006 $ AqB001. Migration of human colon cancer (HT29) cells was assessed with a wound-closure assay in the presence of a mitotic inhibitor. AqB011 and AqB007 significantly reduced migration rates of AQP1-positive HT29 cells without affecting viability. The order of potency for AQP1 ion channel block matched the order for inhibition of cell migration, as well as in silico modeling of the predicted order of energetically favored binding. Docking models suggest that AqB011 and AqB007 interact with the intracellular loop D domain, a region involved in AQP channel gating. Inhibition of AQP1 ionic conductance could be a useful adjunct therapeutic approach for reducing metastasis in cancers that upregulate AQP1 expression.

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Section: Introductionmentioning

confidence: 99%

Bumetanide Derivatives AqB007 and AqB011 Selectively Block the Aquaporin-1 Ion Channel Conductance and Slow Cancer Cell Migration

et al. 2015

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“…Recently, various studies have focused on the association of AQPs with carcinoma and reported that several types of cancer express AQP-1, which may be involved in carcinogenesis and tumor progression [14]- [19]. These observations suggested a potential role of AQP-1 in BTC.…”

Section: Discussionmentioning

confidence: 99%

Expression Analysis of Aquaporin-1 (Aqp-1) in Human Biliary Tract Carcinoma

Sekine¹,

Okumura²,

Nagata³

et al. 2016

JCT

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Background: Aquaporins (AQPs) are important in controlling bile water secretion. AQP is related to the invasion and metastasis of cancer. However, the relationship of biliary tract cancer is not clear. The role of AQP-1 in cancer cell is also unknown. Methhods: We analyzed AQP-1 expression using tissue microarray (TMA) in 99 samples immunohistochemically (50 gallbladder carcinoma, 39 bile duct carcinoma and 10 Papilla Vater carcinoma patients who underwent surgery at our department from 1997 to 2011). Gene expressions were evaluated by the combination of the immunohistological intensity and distribution. The expression level is compared to the clinico-pathological data of the patients. Results: In the TMA, depth of tumor invasion and histological type are associated with AQP-1 expression. The group of patients with high AQP-1 expression is associated with higher rates of disease specific survival (log-rank p = 0.013). Cox's proportional hazard model reveals that AQP-1 expression is an independent prognostic factor (RR, 0.324; p = 0.001) in multivariate analysis. There is a correlation between AQP-1 expression and tumor invasion. Conclusions: These observations of this study suggest that AQP-1 expression may be favorable biomarkers associated with prognosis and tumor invasion in biliary tract carcinoma.

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“…High AQP1 expression has been shown as an independent predictive value for poor outcome. 16,17,24 Aquaporin 1-expressing tumor cells were also showed increased plasma membrane osmotic water permeability and accelerated migration. 13 In our series of 62 hilCC, proportional hazard regression analysis (Table 2) showed that AQP1 expression was an independent significant predictor of survival (P < .01).…”

Section: Discussionmentioning

confidence: 99%

“…Experimental results from AQP1-null mice also greatly showed reduced tumor growth and improved survival (compared with wild-type mice) when implanted subcutaneously with tumor cells, 9 and in vitro studies indicated the same results. 16,17,24 A possible reason is that AQP1 in tumor cells allow water to rapidly penetrate into the growing tumor mass and tumor AQP1 expression may thus cause tumor expansion by exacerbating tumor-associated edema that might be correlated with poor prognosis. In this clinical survey on AQP1 expression in vitro, we found strong AQP1 expression is an independent indicator for an adverse prognosis in hilCC.…”

Section: Discussionmentioning

confidence: 99%

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Elevated AQP1 Expression Is Associated With Unfavorable Oncologic Outcome in Patients With Hilar Cholangiocarcinoma

et al. 2016

Technol Cancer Res Treat

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Background: Hilar cholangiocarcinomas are malignant tumors with a poor prognosis. An early prediction of prognosis for patients may help us determine treatment strategies. Aquaporin 1 is a cell membrane channel involved in water transport, cell motility, and proliferation. Increasing evidences showed that aquaporin 1 played a role in tumor prognosis and diagnosis. The purpose of this study is to evaluate the role of aquaporin 1 in hilar cholangiocarcinoma. Methods: Here, we analyzed messenger RNA expression data of genes function as bile secretion in a data set of 169 samples using the R2 bioinformatic platform (http://r2.amc.nl). Quantitative polymerase chain reaction was performed to verify the gene expression in 17 hilar cholangiocarcinoma samples. Immunohistochemistry was also performed in a series of specimens from 62 hilar cholangiocarcinoma tissues, and its clinical significance was assessed by clinical correlation and Kaplan-Meier analyses. Results: All data were analyzed using the R2 web application, aquaporin 1 was selected for further analysis. The significant expression variation of aquaporin 1 among 17 cases with cholangiocarcinoma was also found using quantitative polymerase chain reaction. The expression level of aquaporin 1 protein significantly correlated with tumor-node-metastasis stage (P ¼ .002) and overall survival time (P ¼ .010). Higher aquaporin 1 expression indicated poor prognostic outcomes (P <.05, log-rank test). Multivariate analysis also showed strong aquaporin 1 protein expression was an independent adverse prognosticator in hilar cholangiocarcinoma (P ¼ .002). Conclusion: This study highlighted the prognostic value of aquaporin 1 in hilar cholangiocarcinoma. Strong aquaporin 1 expression predicts poor survival, regardless of pathological features. Immunohistochemical detection of aquaporin 1, as a prognostic marker, may contribute to predicting clinical outcome for patients with hilar cholangiocarcinoma.

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Expression of aquaporin-1 is a poor prognostic factor for stage II and III colon cancer

Cited by 58 publications

References 18 publications

Bumetanide Derivatives AqB007 and AqB011 Selectively Block the Aquaporin-1 Ion Channel Conductance and Slow Cancer Cell Migration

Bumetanide Derivatives AqB007 and AqB011 Selectively Block the Aquaporin-1 Ion Channel Conductance and Slow Cancer Cell Migration

Expression Analysis of Aquaporin-1 (Aqp-1) in Human Biliary Tract Carcinoma

Elevated AQP1 Expression Is Associated With Unfavorable Oncologic Outcome in Patients With Hilar Cholangiocarcinoma

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