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

Okura, Ryoichi; Fujihara, Shintaro; Iwama, Hisakazu; Morishita, Asahiro; Chiyo, Taiga; Watanabe, Miwako; Hirose, Kenichi; Kobayashi, Kiyoyuki; Fujimori, Takahiro; Kato, Kiyohito; Kamada, Hideki; Kobara, Hideki; Mori, Hideki; Niki, Toshiro; Hirashima, Mitsuomi; Okano, Keiichi; Suzuki, Yasuyuki; Masaki, Tsutomu

doi:10.3892/ol.2017.7316

Cited by 13 publications

(12 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Whereas high galectin-9 expression was associated with reduced survival in lung cancer, increased expression was associated with improved survival in hepatocellular carcinoma, gastric and colorectal cancer and also with a low metastatic potential in breast cancer [17][18][19][20][21]. Notably, in pancreatic cancer cells galectin-9 has been shown to induce apoptosis [22]. However, galectin-9 had no significant effect on AsPC-1 cell proliferation.…”

Section: Discussionmentioning

confidence: 98%

Detection of pancreatic ductal adenocarcinoma with galectin-9 serum levels

et al. 2020

View full text Add to dashboard Cite

Pancreatic ductal adenocarcinoma (PDAC) responds poorly to checkpoint blockade, such as anti-CTLA-4 and anti-PD-1. Galectin-9, a β-galactoside-binding lectin, promotes immune suppression through T-cell inhibition, and programming of tolerogenic macrophages. Of all cancers tested, PDAC showed the highest expression of LGALS9 (galectin-9) mRNA. We analyzed formalin-fixed and paraffin-embedded specimens from 83 patients with PDAC stained for galectin-9. Using flow cytometry, we determined galectin-9 expression on immune cells from tumor and matched blood samples from 12 patients with resectable PDAC. Furthermore, we analyzed galectin-9 serum levels by enzyme-linked immunosorbent assay using serum samples from 70 patients with PDAC, from 36 individuals with benign pancreatic disease, and from 28 healthy controls. Galectin-9 was highly expressed in human PDAC compared with normal pancreas and present on both tumor and immune cells. Tumor-infiltrating immune cells, especially CD3 + T cells, showed upregulation of galectin-9 compared with immune cells from matched blood. Blood γδ T cells from PDAC patients had higher galectin-9 expression than γδ T cells from healthy individuals. Galectin-9 polarized macrophages toward a protumoral M2 phenotype leading to suppressed T-cell cytokine secretion. Furthermore, serum concentration of galectin-9 was able to discriminate PDAC from benign pancreatic disease and healthy individuals, and was prognostic for stage IV patients. Galectin-9 is a new biomarker for the detection of PDAC.

show abstract

Section: Discussionmentioning

confidence: 98%

Detection of pancreatic ductal adenocarcinoma with galectin-9 serum levels

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Another possible explanation involves Gal-9 and its capability of inducing apoptosis. It is reported that addition of recombinant Gal-9 induced apoptosis of various malignant cells, such as hematological malignant cells ( Kobayashi et al, 2010 , 2015 ), melanoma cells ( Kageshita et al, 2002 ; Wiersma et al, 2012 ) and gastrointestinal cells ( Tadokoro et al, 2016 , 2017 ; Okura et al, 2018 ). Further experiments performed in mouse models of leukemia ( Kobayashi et al, 2010 ), myeloma ( Kuroda et al, 2010 ) and hepatobiliary carcinoma ( Fujita et al, 2015 ; Tadokoro et al, 2016 ) have demonstrated that treatment with recombinant Gal-9 prevents tumor progression by inducing apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Galectin-9 Expression Predicts Favorable Clinical Outcome in Solid Tumors: A Systematic Review and Meta-Analysis

et al. 2018

View full text Add to dashboard Cite

Background and Objective: Galectin-9 (Gal-9) is one of the galectin family members which are known as proteins with β-galactoside-binding affinity. Accumulative evidence suggest that Gal-9 plays multifaceted roles in tumor biology. However, the prognostic significance of Gal-9 in solid cancer patients remains controversial. The objective of the study was to clarify the prognostic significance of Gal-9 in solid tumors via meta-analysis.Methods: We searched PubMed, Embase and the Cochrane library for studies that report the correlation between Gal-9 expression and prognosis or clinicopathological parameters in solid cancer patients from inception to October 2017, with no language restriction. We calculated pooled hazard ratio (HR) and 95% confidence interval (CI) to investigate the prognostic significance of Gal-9 expression in solid tumors. We also calculated Odds ratio (OR) to explore the association between Gal-9 expression and clinicopathological features.Results: We included Fourteen studies with 2326 patients in our meta-analysis. The synthetic results revealed that high Gal-9 expression indicated improved overall survival (OS; HR = 0.70, 95% CI = 0.51–0.71, P = 0.006) but had no correlation with disease-free survival (DFS)/recurrence-free survival (RFS) (HR = 0.85, 95% CI = 0.51–1.41, P = 0.527) in solid tumors. In stratified analyses, high Gal-9 expression was significantly correlated with improved OS in hepatocellular carcinoma and colon cancer and with improved DFS/RFS in gastric cancer and non-small cell lung cancer. In addition, ethnicity and the method of data extraction didn’t affect the positive prognostic values of high Gal-9 expression. Moreover, high Gal-9 expression was significantly correlated with a smaller depth of invasion (TI/TII vs. TIII/TIV, OR = 2.80, 95% CI = 1.97–3.96, P < 0.001), an earlier histopathological stage (I/II vs. III/IV, OR = 3.00, 95% CI = 2.04–4.42, P < 0.001), negative lymph node metastasis (Presence vs. Absence, OR = 0.47, 95% CI = 0.25–0.89, P = 0.020) and negative distal tumor metastasis (Presence vs. Absence, OR = 13.85, 95% CI = 3.50–54.76, P < 0.001).Conclusion: Gal-9 expression indicates beneficial outcome in patients with solid tumors and is correlated with the pathogenesis of solid tumors. Gal-9 may serve as a prognostic biomarker and an emerging therapeutic target against solid tumors.

show abstract

“…Due to the limited number of studies about galectin-4 and galectin-9, their biological behaviours and underlying mechanisms in malignancies still remain controversy. Galectin-9 was found to suppress the proliferation of pancreatic cancer cell lines, and metastatic liver cancer cell lines [55, 56]. Conversely, higher serum galectin-9 was observed in PDAC patients [57].…”

Section: Discussionmentioning

confidence: 99%

Prognostic and diagnostic significance of galectins in pancreatic cancer: a systematic review and meta-analysis

et al. 2019

View full text Add to dashboard Cite

BackgroundGalectins constitute a family of β-galactoside-binding proteins, which influence various hallmarks of pancreatic cancer, including cell proliferation, invasion and migration; immune escape; and angiogenesis. Although many studies have concentrated on the role of galectins in pancreatic cancer, the results remain controversial. Hence, we performed a comprehensive meta-analysis to clarify the precise diagnostic and prognostic value of galectins in pancreatic cancer.MethodsPubMed/MEDLINE, EMBASE and Web of Science were used to search related published literature up to July 2019. Pooled hazard ratios (HRs), diagnostic accuracy variables and related 95% confidence intervals (CIs) were calculated using STATA 14.0 software.ResultsEleven studies including 1227 participants met our inclusion criteria. High expression of galectin family was not correlated with overall survival (OS) in pancreatic cancer (HR, 1.19; 95% CI 0.67–2.11). According to subgroup analysis, high levels of galectin-1 were significantly correlated with worse OS in pancreatic cancer (HR, 4.77; 95% CI 2.47–9.21), while high levels of tandem-repeat galectins (galectin-4 or galectin-9) predicted both better OS (HR, 0.63; 95% CI 0.46–0.86) and disease-free survival (DFS) (HR, 0.63; 95% CI 0.48–0.83). The expression levels of galectin-3 did not directly correlate with prognosis (HR, 0.99; 95% CI 0.40–2.46). The pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratios of galectin-3 were 0.64 (95% CI 0.41–0.82), 0.76 (95% CI 0.59–0.88), 2.70 (95% CI 1.21–6.1), and 0.47 (95% CI 0.23–0.98), respectively. The area under the curve (AUC) of galectin-3 was 0.77.ConclusionTaken together, our results suggest that high expression of galectin-1 and low levels of galectin-4 or galectin-9 are predictors of worse prognosis in pancreatic cancer patients. The expression of galectin-3 was not directly related to OS and other clinical characteristics. Although galectin-3 exhibited some diagnostic value in patients with pancreatic cancer in this meta-analysis, clinical application prospects remain to be validated. Further studies are warranted to confirm and strengthen these findings.

show abstract

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

Cited by 13 publications

References 42 publications

Detection of pancreatic ductal adenocarcinoma with galectin-9 serum levels

Detection of pancreatic ductal adenocarcinoma with galectin-9 serum levels

Galectin-9 Expression Predicts Favorable Clinical Outcome in Solid Tumors: A Systematic Review and Meta-Analysis

Prognostic and diagnostic significance of galectins in pancreatic cancer: a systematic review and meta-analysis

Contact Info

Product

Resources

About