Therapeutic potential of Galectin‐9 in human disease

Wiersma, Valerie R.; Bruyn, Marco de; Helfrich, Wijnand; Bremer, Edwin

doi:10.1002/med.20249

Cited by 135 publications

(128 citation statements)

References 109 publications

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“…Interestingly, Gal-9 has been tested as a potential therapeutic agent for various autoimmune diseases (7) and allergic diseases (8). Furthermore, it has been reported that Gal-9 suppresses the cell proliferation and tumor growth of various human cancer types (9,10), such as melanoma (11) and chronic myelogenous leukemia (12). We have previously shown that Gal-9 suppressed the cell proliferation and tumor growth of human hepatocellular carcinoma (HCC) and cholangiocarcinoma by inducing apoptosis, and we have identified several microRNAs (miRNAs) that are associated with the antitumor effect of Gal-9 (13,14).…”

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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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: 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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“…The study of Kadowaki T et al confirmed that Gal-9 signaling prolonged the survival of tumor-bearing mice (Kadowaki et al, 2012). In many solid cancers, the loss of Gal-9 expression is closely associated with metastatic progression (Wiersma et al, 2011). It was supposed that Gal-9 was involved in the suppression of tumor cell metastasis (Atsuya et al, 2008).…”

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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“…T cell hemostasis, cell aggregation and metastasis is well known (14,15). Previous findings suggest that Gal-9 inhibits the proliferation of hematologic malignancies, including multiple myeloma (18) and chronic myeloid leukemia (19), and significantly retards the tumor growth of myeloma xenografts in mice (18).…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have uncovered additional mechanisms by which T cell immunoglobulin mucin-3, a receptor for Gal-9, negatively regulates T cell responses by promoting CD8+ T cell exhaustion and inducing the expansion of myeloid-derived suppressor cells (14,15 immunity by inducing a subset of macrophages and dendritic cells and activating tumor-specific CTLs and NK cells. Recombinant Gal-9 induced apoptosis in various T cell leukemic cell lines in a dose-dependent and functional CRD-dependent manner (16,17).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA profiles during galectin‑9‑induced apoptosis of pancreatic cancer cells

et al. 2017

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Abstract. Pancreatic cancer is the eighth-leading cause of cancer-associated mortality in males and the ninth-leading cause in females worldwide. Even when diagnosed early enough to be potentially resectable, the prognosis of invasive pancreatic cancer is poor. Galectin-9 (Gal-9) is a tandem-repeat type galectin that has recently been demonstrated to possess an anti-proliferative effect on cancer cells. Therefore, the present study evaluated the effects of Gal-9 on the proliferation of human pancreatic cancer cells and examined the microRNAs that are associated with the antitumor effects of Gal-9. Gal-9 suppressed the proliferation of multiple pancreatic cancer cell lines. In addition, Gal-9 treatment increased the levels of caspase-cleaved keratin 18 and the expression of cytochrome c in pancreatic cancer cell lines. This data suggests that Gal-9 induces intrinsic apoptosis in pancreatic cancer cell lines through the caspase-dependent and caspase-independent pathways. In addition, Gal-9 reduced the expression levels of phosphorylated epidermal growth factor receptor and numerous receptor tyrosine kinases (RTKs). In conclusion, Gal-9 may suppress the growth of human pancreatic cancer cells in vitro. These findings suggest that Gal-9 may be a new therapeutic agent for the treatment of pancreatic cancer.

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Therapeutic potential of Galectin‐9 in human disease

Cited by 135 publications

References 109 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

MicroRNA profiles during galectin‑9‑induced apoptosis of pancreatic cancer cells

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