Galectin-9 in physiological and pathological conditions

Hirashima, Mitsuomi; Kashio, Yumiko; Nishi, Nozomu; Yamauchi, Akira; Imaizumi, Tadaatsu; Kageshita, Toshiro; Saita, Naoki; Nakamura, Takanori

doi:10.1023/b:glyc.0000014090.63206.2f

Cited by 165 publications

(135 citation statements)

References 32 publications

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“…Accordingly, the data from the present study indicated that the squamous and adenosquamous forms of GBC were more resistant to Gal-9 treatment due to their poorly differentiated phenotype compared to well-to-moderately differentiated GBC types. Gal-9, a tandem-repeat-type galectin family member that consists of two carbohydrate recognition domains connected by a linker peptide (27), was first described as an eosinophil chemoattractant (4,28). Further research showed that Gal-9 induces apoptosis in T-cells and stimulates regulatory T-cell activity (5-7).…”

Section: Discussionmentioning

confidence: 99%

“…Galectin-9 (Gal-9) is a β-galactoside-binding lectin of the galectin family; this protein is involved in various biological processes, including cell aggregation, adhesion, chemoattraction, and apoptosis (4). The functions of Gal-9 have been reported to include the induction of apoptosis in T-cells, particularly CD4 + Th1 and Th17 cells, and the stimulation of regulatory T-cell activity (5-7).…”

Section: Introductionmentioning

confidence: 99%

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Galectin-9: An anticancer molecule for gallbladder carcinoma

Tadokoro

Morishita

Fujihara

et al. 2016

International Journal of Oncology

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Abstract. Gallbladder cancer (GBC) is the most common and aggressive type of biliary tract cancer. There are various histological types of GBC, and the vast majority of GBC cases are adenocarcinomas. Squamous and adenosquamous carcinomas are rare GBC subtypes that are traditionally considered to be more aggressive and to be associated with a poorer prognosis than adenocarcinoma. Galectin-9 (Gal-9), a tandem-repeattype galectin, has been reported to induce apoptosis-mediated elimination of various cancers, including hepatocellular carcinoma, cholangiocarcinoma, and hematologic malignancies. Therefore, we investigated the antitumor effects of Gal-9 on GBC in vitro and in vivo. In our in vitro experiments, Gal-9 suppressed cell proliferation in various GBC cell lines but not in the OCUG-1 cell line, which represents a poorly differentiated type of adenosquamous carcinoma. Gal-9 induced the apoptosis of Gal-9-sensitive GBC cells by increasing the levels of caspase-cleaved keratin 18 and phosphorylated p53. However, Gal-9 did not affect the expression of various cell cycle-related proteins. In addition, Gal-9 suppressed tumor growth by implanted human GBC cells in a xenograft model. Furthermore, Gal-9 induced the phosphorylation of the Ephrin type-B receptor, and the microRNA (miRNA) expression profile was markedly altered by Gal-9. Based on these results, various miRNAs might contribute to the suppression of tumor growth. Our data reveal that Gal-9 suppresses the growth of GBC, possibly by inducing apoptosis and altering miRNA expression. Thus, Gal-9 might serve as a therapeutic agent for the treatment of GBC.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Galectin-9: An anticancer molecule for gallbladder carcinoma

Tadokoro

Morishita

Fujihara

et al. 2016

International Journal of Oncology

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“…is a member of them, and it was first identified as an eosinophil chemoattractant and activation factor (Matsumoto et al, 1998;Matsushita et al, 2000; Zhao-Yang Zhang 1,2 , Jia-Hong Dong 2 *, Yong-Wei Chen 2 , Xian-Qiang Wang 2 , Chong-Hui Li 2 , Jian Wang 2 , Guo-Qiang Wang 2 , Hai-Lin Li 2 , Xue-Dong Wang 2 Matsumoto et al, 2002;Saita et al, 2002). Subsequent studies revealed that Gal-9, similar to other galectins, modulated a variety of biological functions, such as cell aggregation and adhesion, apoptosis of tumor cells, and others (Asakura et al, 2002;Hirashima et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Galectin-9 Acts as a Prognostic Factor with Antimetastatic Potential in Hepatocellular Carcinoma

Zhang¹,

Dong²,

Chen³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Considerable research has been conducted concerning galectin-9 and carcinomas, but little information is available about any relation with the hepatocellular carcinoma. In this study, we employed a small interfering RNA (siRNA) targeting galectin-9 to down-regulate the expression in HepG2 cells. As a result, after galectin-9 expression was reduced, cell aggregation was suppressed, while other behaviour such as the proliferation, adhesion and invasion to ECM, cell-endothelial adhesion and transendothelial invasion of the cells were markedly enhanced. When tumors of 200 patients with hepatocellular carcinoma were tested for galectin-9 expression by immunohistochemistry, binding levels demonstrated intimate correlations with the histopathologic grade, lymph node metastasis, vascular invasion and intrahepatic metastasis (P<0.05). Moreover, survival analysis indicated that patients with galectin-9 expression had much longer survival time than those with negative lesions, and the Log-rank test indicated that this difference was statistical significant (P<0.0001). The Cox proportional hazards model suggested that negative galectin-9 expression in hepatocellular carcinoma represented a significant risk factor for patient survival. We propose that galectin-9 might be a new prognostic factor with antimetastatic potential in patients with hepatocellular carcinoma.

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“…Among 14 mammalian galectins, galectin-9 (Gal9) has been shown to possess the anticancer properties by regulating various cellular functions, such as cell adhesion, cell proliferation, or apoptosis (8)(9)(10)(11)(12). These prompted us to investigate whether Gal9 can have an anti-CML effect through signaling cascades distinct from the pathway used by Bcr-Abl TKIs or by other commonly used anticancer agents.…”

Section: Introductionmentioning

confidence: 99%

Targeting Activating Transcription Factor 3 by Galectin-9 Induces Apoptosis and Overcomes Various Types of Treatment Resistance in Chronic Myelogenous Leukemia

Kuroda

Yamamoto

Nagoshi

et al. 2010

Molecular Cancer Research

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Tyrosine kinase inhibitors (TKI) against Bcr-Abl are the first-line therapeutics for chronic myelogenous leukemia (CML). However, the resistance to Bcr-Abl TKIs is induced in leukemic cells not only by loss of sensitivity to TKIs through Bcr-Abl-related molecular mechanisms but also by loss of addiction to Bcr-Abl TK activity by acquiring Bcr-Abl-unrelated additional oncogenic mutations. Therefore, the identification of an additional therapeutic target has been anticipated for achievement of a complete cure and to overcome resistance to treatment. We here showed that modified human Galectin-9 (hGal9), a lectin that show specific affinity for β-galactosides, inhibits the proliferation of five CML-derived cell lines by inducing apoptosis at their IC 50 s from 17.5 to 164.9 nmol/L. Our study revealed that activating transcription factor 3 (ATF3), a member of the ATF/ cAMP-responsive element binding protein family transcription factors, is the critical mediator for cell killing by hGal9, and that Noxa is one of the downstream effector molecules of ATF3. Bim, on the other hand, the BH3-only protein essential for apoptosis by Bcr-Abl TKIs, was not associated with hGal9-induced cell death. ATF3-mediated cell death by hGal9 was not hampered by the absence of p53, the presence of mutant Abl T315I , or by P-glycoprotein overexpression. In addition, hGal9 showed the additive growth-inhibitory effect with imatinib on CML cell lines.

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Galectin-9 in physiological and pathological conditions

Cited by 165 publications

References 32 publications

Galectin-9: An anticancer molecule for gallbladder carcinoma

Galectin-9: An anticancer molecule for gallbladder carcinoma

Galectin-9 Acts as a Prognostic Factor with Antimetastatic Potential in Hepatocellular Carcinoma

Targeting Activating Transcription Factor 3 by Galectin-9 Induces Apoptosis and Overcomes Various Types of Treatment Resistance in Chronic Myelogenous Leukemia

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