Possible role of galectin‐9 in cell aggregation and apoptosis of human melanoma cell lines and its clinical significance

Kageshita, Toshiro; Kashio, Yumiko; Yamauchi, Akira; Seki, Masako; Abedin, Mohammad J.; Nishi, Nozomu; Shoji, Hiromichi; Nakamura, Takanori; Ono, Tomomichi; Hirashima, Mitsuomi

doi:10.1002/ijc.10436

Cited by 168 publications

(184 citation statements)

References 40 publications

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“…In other words, the expression of Gal-9 perhaps made it difficult for the tumor cells to detach from primary site. It was consistent with the study of Irie et al (2005) that exogenously added recombinant galectin-9 induced aggregation of breast cancer cells and the study of Kageshita et al (2002) that Gal-9 expression promoted malignant melanoma cells aggregate. It was likely that in the process of migration, cancer cells should firstly detach from tumor tissue individually, and then migrate into lymphatic or blood vessels and metastasis to distant organs (Irie et al, 2005).…”

Section: Discussionsupporting

confidence: 90%

“…In addition to the anti-metastatic roles of Gal-9 mentioned above, it had been reported that Gal-9 induced apoptosis in T cells (Wada et al, 1997;Tsuchiyama et al, 2000), malignant melanoma cells (Kageshita et al, 2002) and breast cancer cells (Irie et al, 2005), and the pro-apoptotic role was required for galectin-9-induced suppression of melanoma and breast cancers (Kageshita et al, 2002;Irie et al, 2005). Kobayashi et al (2010) confirmed that Gal-9 exhibits anti-myeloma activity through JNK and p38 MAP kinase pathways.…”

Section: Discussionmentioning

confidence: 72%

“…Kageshita et al confirmed that high Gal-9 expression in tumor cells was closely associated with reduced metastasis and low recurrence in patients with malignant melanoma (Kageshita et al, 2002), and similar findings were obtained by Irie et al in breast cancer (Irie et al, 2005). The study of Kadowaki T et al confirmed that Gal-9 signaling prolonged the survival of tumor-bearing mice (Kadowaki et al, 2012).…”

Section: Introductionmentioning

confidence: 63%

“…Irie A et al (2005) confirmed that Gal-9 expression was correlated with histopathologic grade and distant metastasis, and Gal-9 acted as a prognostic role in breast cancer. Kageshita T et al (2002) proved that high Gal-9 expression was inversely correlated with the progression of melanocytic tumors, and high Gal-9 expression in primary melanoma lesions links to a better prognosis.…”

Section: Discussionmentioning

confidence: 98%

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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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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 72%

Section: Introductionmentioning

confidence: 63%

Section: Discussionmentioning

confidence: 98%

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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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“…[4][5][6][7][8][9][10] Moreover, recent studies have indentified anti-cancer properties of galectin-9 against several cancers. [11][12][13][14][15] In this study, we show the anti-multiple myeloma (MM) activity of a recombinant mutant form of human galectin-9 (hGal9) through the activation of c-Jun NH 2 -terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) signaling pathways, those share crucial roles in the survival and death of myeloma cells. 16 …”

Section: Introductionmentioning

confidence: 99%

Galectin-9 exhibits anti-myeloma activity through JNK and p38 MAP kinase pathways

et al. 2010

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Galectins constitute a family of lectins that specifically exhibit the affinity for b-galactosides and modulate various biological events. Galectin-9 is a tandem-repeat type galectin with two carbohydrate recognition domains and has recently been shown to have an anti-proliferative effect on cancer cells. We investigated the effect of recombinant protease-resistant galectin-9 (hGal9) on multiple myeloma (MM). In vitro, hGal9 inhibited the cell proliferation of five myeloma cell lines examined, including a bortezomib-resistant subcell line, with IC 50 between 75.1 and 280.0 nM, and this effect was mediated by the induction of apoptosis with the activation of caspase-8, -9, and -3. hGal9-activated Jun NH 2 -terminal kinase (JNK) and p38 MAPK signaling pathways followed by H2AX phosphorylation. Importantly, the inhibition of either JNK or p38 MAPK partly inhibited the anti-proliferative effect of hGal9, indicating the crucial role of these pathways in the anti-MM effect of hGal9. hGal9 also induced cell death in patient-derived myeloma cells, some with poor-risk factors, such as chromosomal deletion of 13q or translocation t(4;14)(p16;q32). Finally, hGal9 potently inhibited the growth of human myeloma cells xenografted in nude mice. These suggest that hGal9 is a new therapeutic target for MM that may overcome resistance to conventional chemotherapy.

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Beneficial effect of galectin 9 on rheumatoid arthritis by induction of apoptosis of synovial fibroblasts

Seki¹,

Sakata²,

Oomizu³

et al. 2007

Arthritis & Rheumatism

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Objective. To compare the expression of galectin 9 (Gal-9) in synovial tissue (ST) from rheumatoid arthritis (RA) patients and osteoarthritis (OA) patients and to evaluate the effects of Gal-9 on fibroblast-like synoviocytes (FLS) in these patients.Methods. The expression of Gal-9 in ST and FLS was compared using immunohistochemical techniques. Apoptotic cells in RA and OA ST samples were detected by TUNEL assay. Apoptosis of FLS was analyzed by the sub-G 1 method in vitro. The in vivo suppressive effects of Gal-9 on collagen-induced arthritis (CIA) in a mouse model were also elucidated.Results. The percentage of Gal-9-positive cells in ST samples and the amount of Gal-9 in synovial fluid samples were significantly higher in patients with RA than in patients with OA, suggesting the involvement of Gal-9 in the development of RA. Compared with the 2 wild-type Gal-9 forms, stable Gal-9, a mutant protein resistant to proteolysis, significantly induced apoptosis of FLS from RA patients. In contrast, other galectins, such as Gal-1, Gal-3, and Gal-8, did not induce apoptosis or suppress the proliferation of human RA FLS. Stable Gal-9 preferentially induced apoptosis and suppressed the proliferation of RA FLS in vitro. It also induced apoptosis of cells in RA ST implanted into SCID mice in vivo. In a mouse model of CIA, apoptotic cells were detected in the joints of stable Gal-9-treated mice, but not phosphate buffered saline-treated mice, and suppressed CIA characterized by pannus formation with inflammatory cell infiltration and bone/cartilage destruction.Conclusion. Gal-9-induced apoptosis of hyperproliferative RA FLS may play a critical role in the suppression of RA.

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Possible role of galectin‐9 in cell aggregation and apoptosis of human melanoma cell lines and its clinical significance

Cited by 168 publications

References 40 publications

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

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

Galectin-9 exhibits anti-myeloma activity through JNK and p38 MAP kinase pathways

Beneficial effect of galectin 9 on rheumatoid arthritis by induction of apoptosis of synovial fibroblasts

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