Galectin-9: An anticancer molecule for gallbladder carcinoma

Tadokoro, Tomoko; Morishita, Asahiro; Fujihara, Shintaro; Iwama, Hisakazu; Niki, Toshiro; Fujita, Koji; Akashi, Emiko; Mimura, Shima; Oura, Kyoko; Sakamoto, Teppei; Nomura, Takako; Tani, Joji; Miyoshi, Hisaaki; Yoneyama, Hirohito; Himoto, Takashi; Hirashima, Mitsuomi; Masaki, Tsutomu

doi:10.3892/ijo.2016.3347

Cited by 27 publications

(30 citation statements)

References 37 publications

(50 reference statements)

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“…Depending on the nature and distribution of IgE receptors, different functions might be envisaged. Galectin‐3 is well recognized for its contribution to tumour progression and metastasis development , while galectin‐9 seems to have antiproliferative effects . The trimeric FcεRI(αγ2) showed membranous and cytoplasmic expression in intestinal epithelial cells and a prominent FcεRI α‐chain expression was also found in the Paneth cells of patients with cancer of the proximal colon.…”

Section: Ige Receptor Expression On Immune Cells and Epithelial Cellsmentioning

confidence: 99%

AllergoOncology – the impact of allergy in oncology: EAACI position paper

Jensen‐Jarolim

Bax

Bianchini

et al. 2017

Allergy

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Th2 immunity and allergic immune surveillance play critical roles in host responses to pathogens, parasites and allergens. Numerous studies have reported significant links between Th2 responses and cancer, including insights into the functions of IgE antibodies and associated effector cells in both anti-tumour immune surveillance and therapy. The interdisciplinary field of AllergoOncology was given Task Force status by the European Academy of Allergy and Clinical Immunology in 2014. Affiliated expert groups focus on the interface between allergic responses and cancer, applied to immune surveillance, immunomodulation and the functions of IgE-mediated immune responses against cancer, to derive novel insights into more effective treatments. Co-incident with rapid expansion in clinical application of cancer immunotherapies, here we review the current state-of-the-art and future translational opportunities, as well as challenges in this relatively new field. Recent developments include improved understanding of Th2 antibodies, intra-tumoural innate allergy effector cells and mediators, IgE-mediated tumour antigen cross-presentation by dendritic cells, as well as immunotherapeutic strategies such as vaccines and recombinant antibodies, and finally, the management of allergy in daily clinical oncology. Shedding light on the cross-talk between allergic response and cancer is paving the way for new avenues of treatment.

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Section: Ige Receptor Expression On Immune Cells and Epithelial Cellsmentioning

confidence: 99%

AllergoOncology – the impact of allergy in oncology: EAACI position paper

Jensen‐Jarolim

Bax

Bianchini

et al. 2017

Allergy

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“…Clinical symptoms arise late in the course of the disease, 30-40 years after asbestos exposure, when the efficacy of therapeutic interventions is limited. In this study, we found that human MM tumors express high levels of galectin-9, a lectin that recently emerged as a promising target for cancer immunotherapy due to its dual role in cancer cell apoptosis [5][6][7][8][9][10][11] and TAMs differentiation. 14,38 We generated and tested a novel P4D2 mAb that binds galectin-9 C-terminal CRD and shows unique agonistic properties with recombinant galectin-9 in inducing cancer cell apoptosis and in modulating macrophage polarization.…”

Section: Discussionmentioning

confidence: 99%

“…[28][29][30] Treatment with recombinant galectin-9 has been demonstrated to interact with these lattice structures and promote apoptosis in different types of tumor cells. [5][6][7][8][9][10][11] In our preliminary experiments, we observed that both human and mouse MM cells express surface galectin-9 ( Supplementary Figure 1a-c) and therefore investigated if P4D2 and P1D9 mAbs could mimic the apoptotic effect induced by recombinant galectin-9. We assayed two human MM cell lines (Mill and ROB) and two mouse MM cell lines (CRH5 and EOH6).…”

Section: P4d2 Has Agonistic Properties and Induces Apoptosis Of MM Cellsmentioning

confidence: 99%

“…[1][2][3][4] Both in vitro and in vivo studies showed that recombinant galectin-9 induces apoptosis of tumor cells, such as hematologic malignant cells, 5,6 melanoma, 7 and gastrointestinal tumors. [8][9][10][11] Studies with immune cells suggest that galectin-9 could also modulate cells of the tumor microenvironment as T cells, 12 B cells, and macrophages, 13,14 although it is unclear if this modulation leads to an antitumor or protumor effect. 15,16 MM is a lethal cancer linked to asbestos that is increasing in incidence worldwide.…”

Section: Introductionmentioning

confidence: 99%

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Targeting the C-terminus of galectin-9 induces mesothelioma apoptosis and M2 macrophage depletion

et al. 2019

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Galectin-9 has emerged as a promising biological target for cancer immunotherapy due to its role as a regulator of macrophage and T-cell differentiation. In addition, its expression in tumor cells modulates tumor cell adhesion, metastasis, and apoptosis. Malignant mesothelioma (MM) is an aggressive neoplasm of the mesothelial cells lining the pleural and peritoneal cavities, and in this study, we found that both human MM tissues and mouse MM cells express high levels of galectin-9. Using a novel monoclonal antibody (mAb) (Clone P4D2) that binds the C-terminal carbohydrate recognition domain (CRD) of galectin-9, we demonstrate unique agonistic properties resulting in MM cell apoptosis. Furthermore, the P4D2 mAb reduced tumor-associated macrophages differentiation toward a protumor phenotype. Importantly, these effects exerted by the P4D2 mAb were observed in both human and mouse in vitro experiments and not observed with another antigalectin-9 specific mAb (clone P1D9) that engages the N-terminus CRD of galectin-9. In syngeneic murine models of MM, P4D2 mAb treatment inhibited tumor growth and improved survival, with tumors from P4D2-treated mice exhibited reduced infiltration of tumor-associated M2 macrophages. This was consistent with an increased production of inducible nitric oxide synthase, which is a major enzyme-regulating macrophage inflammatory response to cancer. These data suggest that using an antigalectin 9 mAb with agonistic properties similar to those exerted by galectin-9 may provide a novel multitargeted strategy for the treatment of mesothelioma and possibly other galectin-9 expressing tumors. ARTICLE HISTORY

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“…Galectin-9 has been reported to exert anticancer activity in gallbladder cancer by modulation of the miRNA expression profile [125]. On the other hand, in liver cancer, galectin-9 is overexpressed because of miR-22 downregulation.…”

Section: Epigenetic Regulation Of Sugar Binding Molecules: the Galmentioning

confidence: 99%

Epigenetic Bases of Aberrant Glycosylation in Cancer

Dall’Olio

Trinchera

2017

IJMS

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In this review, the sugar portions of glycoproteins, glycolipids, and glycosaminoglycans constitute the glycome, and the genes involved in their biosynthesis, degradation, transport and recognition are referred to as “glycogenes“. The extreme complexity of the glycome requires the regulatory layer to be provided by the epigenetic mechanisms. Almost all types of cancers present glycosylation aberrations, giving rise to phenotypic changes and to the expression of tumor markers. In this review, we discuss how cancer-associated alterations of promoter methylation, histone methylation/acetylation, and miRNAs determine glycomic changes associated with the malignant phenotype. Usually, increased promoter methylation and miRNA expression induce glycogene silencing. However, treatment with demethylating agents sometimes results in silencing, rather than in a reactivation of glycogenes, suggesting the involvement of distant methylation-dependent regulatory elements. From a therapeutic perspective aimed at the normalization of the malignant glycome, it appears that miRNA targeting of cancer-deranged glycogenes can be a more specific and promising approach than the use of drugs, which broad target methylation/acetylation. A very specific type of glycosylation, the addition of GlcNAc to serine or threonine (O-GlcNAc), is not only regulated by epigenetic mechanisms, but is an epigenetic modifier of histones and transcription factors. Thus, glycosylation is both under the control of epigenetic mechanisms and is an integral part of the epigenetic code.

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Galectin-9: An anticancer molecule for gallbladder carcinoma

Cited by 27 publications

References 37 publications

AllergoOncology – the impact of allergy in oncology: EAACI position paper

AllergoOncology – the impact of allergy in oncology: EAACI position paper

Targeting the C-terminus of galectin-9 induces mesothelioma apoptosis and M2 macrophage depletion

Epigenetic Bases of Aberrant Glycosylation in Cancer

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