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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)
  • Published : 2012.06.30

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

References

  1. 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. https://doi.org/10.4049/jimmunol.169.10.5912
  2. 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. https://doi.org/10.1093/glycob/cwn062
  3. Engbring JA, Kleinman HK (2003). The basement membrane matrix in malignancy. J Pathol, 200, 465-70. https://doi.org/10.1002/path.1396
  4. Farazi PA, DePinho RA (2006). Hepatocellular carcinoma pathogenesis: from genes to environment. Nat Rev Cancer, 6, 674-87. https://doi.org/10.1038/nrc1934
  5. 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. https://doi.org/10.1073/pnas.0402669101
  6. Hanahan D, Weinberg RA (2000). The hallmarks of cancer. Cell, 100, 57-70. https://doi.org/10.1016/S0092-8674(00)81683-9
  7. Hann HW, Lee J, Bussard A, et al (2004). Preneoplastic markers of hepatitis B virus-associated hepatocellular carcinoma. Cancer Res, 64, 7329-35. https://doi.org/10.1158/0008-5472.CAN-04-1095
  8. Hirashima M, Kashio Y, Nishi N, et al (2004). Galectin-9 in physiological and pathological conditions. Glycoconj J, 19, 593-600.
  9. Hsu DK, Liu FT (2004). Regulation of cellular homeostasis by galectins. Glycoconj J, 19, 507-15.
  10. Hughes RC (2001). Galectins as modulators of cell adhesion. Biochimie, 83, 667-76. https://doi.org/10.1016/S0300-9084(01)01289-5
  11. 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. https://doi.org/10.1158/1078-0432.CCR-04-0861
  12. 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. https://doi.org/10.1002/ijc.10436
  13. 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. https://doi.org/10.4049/jimmunol.181.11.7660
  14. Kilpatrick DC (2002). Animal lectins: A historical introduction and overview. Biochim Biophys Acta, 1572, 187-97. https://doi.org/10.1016/S0304-4165(02)00308-2
  15. Kim R, Emi M, Tanabe K, et al (2006). Tumor-driven evolution of immunosuppressive networks during malignant progression. Cancer Res, 66, 5527-36. https://doi.org/10.1158/0008-5472.CAN-05-4128
  16. 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. https://doi.org/10.1038/leu.2010.25
  17. 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.
  18. Matsumoto R, Hirashima M, Kita H, et al (2002). Biological activities of ecalectin: a novel eosinophil-activating factor. J Immunol, 168, 1961-67. https://doi.org/10.4049/jimmunol.168.4.1961
  19. 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. https://doi.org/10.1074/jbc.273.27.16976
  20. 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. https://doi.org/10.1074/jbc.275.12.8355
  21. 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. https://doi.org/10.1007/s10585-007-9098-2
  22. Parkin DM, Bray F, Ferlay J, et al (2005). Global cancer statistics, 2002. CA Cancer J Clin, 55, 74-108. https://doi.org/10.3322/canjclin.55.2.74
  23. 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. https://doi.org/10.1016/j.critrevonc.2003.09.006
  24. 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. https://doi.org/10.1158/0008-5472.CAN-09-1096
  25. Saita N, Goto E, Yamamoto T, et al (2002). Association of galectin-9 with eosinophil apoptosis. Int Arch Allergy Immunol, 128, 42-50. https://doi.org/10.1159/000058002
  26. 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. https://doi.org/10.1111/j.1523-1755.2000.00366.x
  27. 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.
  28. 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.
  29. 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. https://doi.org/10.1016/j.clon.2007.09.008
  30. Zou W (2005). Immunosuppressive networks in the tumour environment and their therapeutic relevance. Nat Rev Cancer, 5, 263-74. https://doi.org/10.1038/nrc1586

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