Browse > Article
http://dx.doi.org/10.7314/APJCP.2012.13.6.2503

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

Zhang, Zhao-Yang (Department of Hepatobiliary Surgery, Qilu Hospital of Shandong University)
Dong, Jia-Hong (Department of Hepatobiliary Surgery, Division of Surgery, Chinese PLA General Hospital)
Chen, Yong-Wei (Department of Hepatobiliary Surgery, Division of Surgery, Chinese PLA General Hospital)
Wang, Xian-Qiang (Department of Hepatobiliary Surgery, Division of Surgery, Chinese PLA General Hospital)
Li, Chong-Hui (Department of Hepatobiliary Surgery, Division of Surgery, Chinese PLA General Hospital)
Wang, Jian (Department of Hepatobiliary Surgery, Division of Surgery, Chinese PLA General Hospital)
Wang, Guo-Qiang (Department of Hepatobiliary Surgery, Division of Surgery, Chinese PLA General Hospital)
Li, Hai-Lin (Department of Hepatobiliary Surgery, Division of Surgery, Chinese PLA General Hospital)
Wang, Xue-Dong (Department of Hepatobiliary Surgery, Division of Surgery, Chinese PLA General Hospital)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.13, no.6, 2012 , pp. 2503-2509 More about this Journal
Abstract
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.
Keywords
Galectin-9; hepatocellular carcinoma; metastasis; prognosis;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Matsushita N, Nishi N, Seki M, et al (2000). Requirement of divalent galactoside-binding activity of ecalectin/galectin-9 for eosinophil chemoattraction. J Biol Chem, 275, 8355-60.   DOI
2 Miles FL, Pruitt FL, van-Golen KL, et al (2008). Stepping out of the flow: capillary extravasation in cancer metastasis. Clin Exp Metastasis, 25, 305-24.   DOI
3 Parkin DM, Bray F, Ferlay J, et al (2005). Global cancer statistics, 2002. CA Cancer J Clin, 55, 74-108.   DOI   ScienceOn
4 Pasco S, Ramont L, Maquart FX, et al (2004). Control of melanoma progression by various matrikines from basement membrane macromolecules. Crit Rev Oncol Hematol, 49, 221-33.   DOI
5 Qicheng Zhao, Xiuli Guo, Gerard B Nash, et al (2009). Circulating Galectin-3 Promotes Metastasis by Modifying MUC1 Localization on Cancer Cell Surface. Cancer Res, 69, 6799-806.   DOI
6 Saita N, Goto E, Yamamoto T, et al (2002). Association of galectin-9 with eosinophil apoptosis. Int Arch Allergy Immunol, 128, 42-50.   DOI
7 Tsuchiyama Y, Wada J, Zhang H (2000). Efficacy of galectins in the amelioration of nephrotoxic serum nephritis in Wistar Kyoto rats. Kidney Int, 58, 1941-52.   DOI
8 Wada J, Ota K, Kumar A, et al (1997). Developmental regulation, expression, and apoptotic potential of galectin-9, a $\beta$-galactoside binding lectin. J Clin Invest, 99, 245-61.
9 Wiersma VR, de Bruyn M, Helfrich W, et al (2011). Therapeutic potential of Galectin-9 in human disease. Med Res Rev, doi: 10.1002/med. 20249.
10 Zhang ZY, Xu KS, Wang JS, et al (2008). Integrin alphanvbeta6 acts as a prognostic indicator in gastric carcinoma. Clin Oncol (R Coll Radiol), 20, 61-6.   DOI
11 Asakura H, Kashio Y, Nakamura K, et al (2002). Selective eosinophil adhesion to fibroblast via IFN-$\gamma$-induced galectin-9. J Immunol, 169, 5912-18.   DOI
12 Atsuya N, Keiko N, Souichi O, et al (2008). Galectin-9 suppresses tumor metastasis by blocking adhesion to endothelium and extracellular matrices. Glycobiology, 18, 735-44.   DOI
13 Engbring JA, Kleinman HK (2003). The basement membrane matrix in malignancy. J Pathol, 200, 465-70.   DOI
14 Farazi PA, DePinho RA (2006). Hepatocellular carcinoma pathogenesis: from genes to environment. Nat Rev Cancer, 6, 674-87.   DOI   ScienceOn
15 Gray CA, Adelson DL, Bazer FW, et al (2004). Discovery and characterization of an epithelial-specific galectin in the endometrium that forms crystals in the trophectoderm. Proc Natl Acad Sci USA, 101, 7982-7.   DOI
16 Hanahan D, Weinberg RA (2000). The hallmarks of cancer. Cell, 100, 57-70.   DOI   ScienceOn
17 Hann HW, Lee J, Bussard A, et al (2004). Preneoplastic markers of hepatitis B virus-associated hepatocellular carcinoma. Cancer Res, 64, 7329-35.   DOI
18 Hirashima M, Kashio Y, Nishi N, et al (2004). Galectin-9 in physiological and pathological conditions. Glycoconj J, 19, 593-600.
19 Hsu DK, Liu FT (2004). Regulation of cellular homeostasis by galectins. Glycoconj J, 19, 507-15.
20 Zou W (2005). Immunosuppressive networks in the tumour environment and their therapeutic relevance. Nat Rev Cancer, 5, 263-74.   DOI   ScienceOn
21 Hughes RC (2001). Galectins as modulators of cell adhesion. Biochimie, 83, 667-76.   DOI
22 Irie A, Yamauchi A, Kontani K, et al (2005). Galectin-9 as a prognostic factor with antimetastatic potential in breast cancer. Clin Cancer Res, 11, 2962-8.   DOI
23 Kageshita T, Kashio Y, Yamauchi A, et al (2002). Possible role of galectin-9 in cell aggregation and apoptosis of human melanoma cell lines and its clinical significance. Int J Cancer, 99, 809-16.   DOI
24 Keiko N, Tomohiro A, Souichi O, et al (2008). Galectin-9 Increases Tim-3+ Dendritic Cells and CD8+ T Cells and Enhances Antitumor Immunity via Galectin-9-Tim-3 Interactions. J Immunol, 181, 7660-9.   DOI
25 Kilpatrick DC (2002). Animal lectins: A historical introduction and overview. Biochim Biophys Acta, 1572, 187-97.   DOI   ScienceOn
26 Kim R, Emi M, Tanabe K, et al (2006). Tumor-driven evolution of immunosuppressive networks during malignant progression. Cancer Res, 66, 5527-36.   DOI
27 Kobayashi T, Kuroda J, Ashibara E, et al (2010). Galectin-9 exhibits anti-myeloma activity through JNK and p38 MAP kinase pathways. Leukemia, 24, 843-50.   DOI
28 Li N, Lucy W, Herbert C, et al (2009). Down-regulation of Notch1 signaling inhibits tumor growth in human hepatocellular carcinoma. Am J Transl Res, 1, 358-66.
29 Matsumoto R, Hirashima M, Kita H, et al (2002). Biological activities of ecalectin: a novel eosinophil-activating factor. J Immunol, 168, 1961-67.   DOI
30 Matsumoto R, Matsumoto H, Seki M, et al (1998). Human ecalectin, a variant of human galectin-9, is a novel eosinophil chemoattractant produced by T lymphocytes. J Biol Chem, 273, 16976-84.   DOI