Involvement of aquaporin-5 in differentiation of human gastric cancer cells

Watanabe, Tomoko; Fujii, Takuto; Oya, Takeshi; Horikawa, Naoki; Tabuchi, Yoshiaki; Takahashi, Yûji; Morii, Magotoshi; Takeguchi, Noriaki; Tsukada, Kazuhiro; Sakai, Hideki

doi:10.1007/s12576-008-0017-3

Cited by 60 publications

(33 citation statements)

References 29 publications

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“…Watanabe et al reported that exogenous expression of AQP5 significantly increased the differentiated proportion of a human gastric adenocarcinoma cell line [40]. Kong et al described that AQP4 deletion in ANSCs preferentially impaired the neuronal differentiation rather than glial differentiation.…”

Section: Aqp5 Deletion Increases Differentiation Capacity Of Mscsmentioning

confidence: 99%

Increased Differentiation Capacity of Bone Marrow-Derived Mesenchymal Stem Cells in Aquaporin-5 Deficiency

Khan

Gao

et al. 2012

Stem Cells and Development

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Mesenchymal stem cells (MSCs) are adult stem cells with a self-renewal and multipotent capability and express extensively in multitudinous tissues. We found that water channel aquaporin-5 (AQP5) is expressed in bone marrow-derived MSCs (BMMSCs) in the plasma membrane pattern. BMMSCs from AQP5 -/ -mice showed significantly lower plasma membrane water permeability than those from AQP5 + / + mice. In characterizing the cultured BMMSCs from AQP5-/ -and AQP5 + / + mice, we found no obvious differences in morphology and proliferation between the 2 genotypes. However, the multiple differentiation capacity was significantly higher in AQP5 -/ -than AQP5 + / + BMMSCs as revealed by representative staining by Oil Red O (adipogenesis); Alizarin Red S and alkaline phosphatase (ALP; osteogenesis); and type II collagen and Safranin O (chondrogenesis) after directional induction. Relative mRNA expression levels of 3 lineage differentiation markers, including PPARc2, C/EBPa, adipsin, collagen 1a, osteopontin, ALP, collagen 11a, collagen 2a, and aggrecan, were significantly higher in AQP5 -/ --differentiating BMMSCs, supporting an increased differentiation capacity of AQP5BMMSCs. Furthermore, a bone-healing process was accelerated in AQP5 -/ -mice in a drill-hole injury model. Mechanistic studies indicated a significantly lower apoptosis rate in AQP5 -/ -than AQP5 + / + BMMSCs. Apoptosis inhibitor Z-VAD-FMK increased the differentiation capacity to a greater extent in AQP5 + / + than AQP5 -/ -BMMSCs. We conclude that AQP5-mediated high plasma membrane water permeability enhances the apoptosis rate of differentiating BMMSCs, thus decreasing their differentiation capacity. These data implicate AQP5 as a novel determinant of differentiation of BMMSCs and therefore a new molecular target for regulating differentiation of BMMSCs during tissue repair and regeneration.

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Section: Aqp5 Deletion Increases Differentiation Capacity Of Mscsmentioning

confidence: 99%

Increased Differentiation Capacity of Bone Marrow-Derived Mesenchymal Stem Cells in Aquaporin-5 Deficiency

Khan

Gao

et al. 2012

Stem Cells and Development

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“…Overexpression of several AQPs has been observed in different types of human carcinoma [6,7,8,9,10,11,12,13,14]. We previously reported that AQP-5 may be involved in the differentiation of human gastric carcinoma cells [6]. We also analyzed AQP-1, -4, -5, and -8 expression immunohistochemically using tissue microarray (TMA) in 81 biliary tract carcinoma samples [15].…”

Section: Introductionmentioning

confidence: 99%

Role of Aquaporin-5 in Gallbladder Carcinoma

et al. 2013

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Background/Purpose: Aquaporins (AQPs) are important in controlling bile formation. However, the exact role in human gallbladder carcinogenesis has not yet been defined. Methods: AQP-5-expressing gallbladder carcinoma (GBC) cell lines (NOZ) were transfected with anti-AQP-5 small interfering RNA (siRNA). Growth, migration, invasion assay, and drug susceptibility tests were performed. Next, microRNA (miRNA) expression was analyzed by miRNA oligo chip (3D-Gene®). AQP-5 and AQP-5-related miRNA target gene expressions were also analyzed using tissue microarray (TMA) in 44 GBC samples. Results: Treatment with AQP-5 siRNA decreased cell proliferation, migration, and invasion. On the other hand, those cells increased IC₅₀ of gemcitabine. By performing miRNA assays, miR-29b, -200a, and -21 were shown to be highly overexpressed in cells treated with AQP-5 siRNA NOZ. When focusing on miR-21, phosphatase and tensin homolog (PTEN) was found to be a target of miR-21. In the TMA, AQP-5/PTEN coexpression was significantly associated with the depth of invasion and MIB-1 index (p = 0.003, 0.010). Survival of patients with a high AQP-5/PTEN coexpression was longer than that of patients with a low coexpression (p = 0.003). Conclusions: Our result suggested that miR-21 and PTEN may contribute to the role of AQP-5 in GBC. AQP-5 and PTEN cascades are favorable biomarkers of GBC.

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“…We previously reported that AQP-5 may be involved in differentiation of human gastric carcinoma cells, and overexpression of several aquaporins has been reported in different types of human carcinoma (8)(9)(10)(11)(12)(13)(14)(15)(16). However, the role of AQPs in biliary tract carcinogenesis has not yet been clearly defined.…”

Section: Introductionmentioning

confidence: 99%

Prognostic significance of aquaporins in human biliary tract carcinoma

et al. 2012

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Abstract. Aquaporins (AQPs) are important in controlling bile formation, however, the exact role of AQPs in human biliary tract carcinogenesis has not been clearly defined. In this study, we analyzed AQP-1, -4, -5 and -8 expression immunohistochemically using tissue microarrays (TMAs) in 81 samples. (45 gallbladder carcinomas and 36 bile duct carcinomas). The survival of patients with high AQP-5 expression was longer compared to that of patients with low AQP-5 expression (P=0.017). Cox's proportional hazard model revealed that AQP-5 expression was an independent prognostic factor (RR, 0.38; P=0.025). Chi-square analysis revealed that high AQP-5 expression correlated to small tumor size in biliary tract carcinoma patients (P=0.006). With regard to the expression of other AQPs, depth of tumor invasion, histological type and serum carbohydrate antigen 19-9 (CA19-9) were associated with high AQP-1 expression (P=0.039, 0.011 and 0.032). However, AQP-4 and AQP-8 expression had no association with clinicopathological factors. Among the 10 patients who underwent gemcitabine (GEM) plus S-1 postoperative chemotherapy, the group of patients (n=5) with high AQP-5 expression were associated with higher rates of both overall and disease-free survival (log-rank P=0.033, 0.002). In conclusion, the results of this study suggest that AQP-5 expression may be associated with prognosis and drug sensitivity in biliary tract carcinoma.

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Involvement of aquaporin-5 in differentiation of human gastric cancer cells

Cited by 60 publications

References 29 publications

Increased Differentiation Capacity of Bone Marrow-Derived Mesenchymal Stem Cells in Aquaporin-5 Deficiency

Increased Differentiation Capacity of Bone Marrow-Derived Mesenchymal Stem Cells in Aquaporin-5 Deficiency

Role of Aquaporin-5 in Gallbladder Carcinoma

Prognostic significance of aquaporins in human biliary tract carcinoma

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