Cancer Letters
Volume 290, Issue 2 , Pages 204-210 , 28 April 2010

Interferon alpha inhibits hepatocellular carcinoma growth through inducing apoptosis and interfering with adhesion of tumor endothelial cells

  • Ti Zhang

      Affiliations

    • Department of Hepatobiliary Surgery, Cancer Hospital of Tianjin Medical University, Huan Hu Xi Road, Tianjin 300060, PR China
    • ,
  • Hui-Chuan Sun

      Affiliations

    • Liver Cancer Institute and Zhong Shan Hospital of Fudan University, 136 Yi Xue Yuan Road, Shanghai 200032, PR China
    • ,
  • Hong-Yuan Zhou

      Affiliations

    • Department of Hepatobiliary Surgery, Cancer Hospital of Tianjin Medical University, Huan Hu Xi Road, Tianjin 300060, PR China
    • ,
  • Jing-Tao Luo

      Affiliations

    • Department of Hepatobiliary Surgery, Cancer Hospital of Tianjin Medical University, Huan Hu Xi Road, Tianjin 300060, PR China
    • ,
  • Bai-Lin Zhang

      Affiliations

    • Department of Radiotherapy, Cancer Hospital of Tianjin Medical University, Huan Hu Xi Road, Tianjin 300060, PR China
    • ,
  • Peng Wang

      Affiliations

    • Department of Neurosurgery, Cancer Hospital of Tianjin Medical University, Huan Hu Xi Road, Tianjin 300060, PR China
    • ,
  • Lu Wang

      Affiliations

    • Liver Cancer Institute and Zhong Shan Hospital of Fudan University, 136 Yi Xue Yuan Road, Shanghai 200032, PR China
    • ,
  • Lun-Xiu Qin

      Affiliations

    • Liver Cancer Institute and Zhong Shan Hospital of Fudan University, 136 Yi Xue Yuan Road, Shanghai 200032, PR China
    • ,
  • Ning Ren

      Affiliations

    • Liver Cancer Institute and Zhong Shan Hospital of Fudan University, 136 Yi Xue Yuan Road, Shanghai 200032, PR China
    • ,
  • Sheng-Long Ye

      Affiliations

    • Liver Cancer Institute and Zhong Shan Hospital of Fudan University, 136 Yi Xue Yuan Road, Shanghai 200032, PR China
    • ,
  • Qiang Li

      Affiliations

    • Department of Hepatobiliary Surgery, Cancer Hospital of Tianjin Medical University, Huan Hu Xi Road, Tianjin 300060, PR China
    • Tel./fax: +86 22 2335 9904.
    • ,
  • Zhao-You Tang

      Affiliations

    • Liver Cancer Institute and Zhong Shan Hospital of Fudan University, 136 Yi Xue Yuan Road, Shanghai 200032, PR China
    • Corresponding Author InformationCorresponding author. Tel./Fax: +86 21 6403 7181.

Received 15 February 2009 ,Revised 9 September 2009 ,Accepted 14 September 2009.

References 

  1. Llovet JM, Burroughs A, Bruix J. Hepatocellular carcinoma. Lancet. 2003;362:1907–1917
  2. Poon RT, Lau C, Pang R, Ng KK, Yuen J, Fan ST. High serum vascular endothelial growth factor levels predict poor prognosis after radiofrequency ablation of hepatocellular carcinoma: importance of tumor biomarker in ablative therapies. Ann. Surg. Oncol. 2007;14:1835–1845
  3. Wang L, Tang ZY, Qin LX, Wu XF, Sun HC, Xue Q, et al. High-dose and long-term therapy with interferon-alfa inhibits tumor growth and recurrence in nude mice bearing human hepatocellular carcinoma xenografts with high metastatic potential. Hepatology. 2000;32:43–48
  4. Wang L, Wu WZ, Sun HC, Wu XF, Qin LX, Liu YK, et al. Mechanism of interferon alpha on inhibition of metastasis and angiogenesis of hepatocellular carcinoma after curative resection in nude mice. J. Gastrointest. Surg. 2003;7:587–594
  5. Wu WZ, Sun HC, Gao YQ, Li Y, Wang L, Zhou K, et al. Reduction in p48-ISGFgamma levels confers resistance to interferon-alpha2a in MHCC97 cells. Oncology. 2004;67:428–440
  6. Wu WZ, Sun HC, Shen YF, Chen J, Wang L, Tang ZY, et al. Interferon alpha 2a downregulates VEGF expression through PI3 kinase and MAP kinase signaling pathways. J. Cancer Res. Clin. Oncol. 2005;131:169–178
  7. Lin SM, Lin CJ, Hsu CW, Tai DI, Sheen IS, Lin DY, et al. Prospective randomized controlled study of interferon-alpha in preventing hepatocellular carcinoma recurrence after medical ablation therapy for primary tumors. Cancer. 2004;100:376–382
  8. Sun HC, Tang ZY, Wang L, Qin LX, Ma ZC, Ye QH, et al. Postoperative interferon alpha treatment postponed recurrence and improved overall survival in patients after curative resection of HBV-related hepatocellular carcinoma: a randomized clinical trial. J. Cancer Res. Clin. Oncol. 2006;132:458–465
  9. Lo CM, Liu CL, Chan SC, Lam CM, Poon RT, Ng IO, et al. A randomized, Controlled trial of postoperative adjuvant interferon therapy after resection of hepatocellular carcinoma. Ann. Surg. 2007;245:831–842
  10. Bergers G, Benjamin LE. Tumorigenesis and the angiogenic switch. Nat. Rev. Cancer. 2003;3:401–410
  11. Cleaver O, Melton DA. Endothelial signaling during development. Nat. Med. 2003;9:661–668
  12. Zhang T, Sun HC, Xu Y, Zhang KZ, Wang L, Qin LX, et al. Overexpression of platelet-derived growth factor receptor alpha in endothelial cells of hepatocellular carcinoma associated with high metastatic potential. Clin. Cancer Res. 2005;11:8557–8563
  13. Sun FX, Tang ZY, Lui KD, Ye SL, Xue Q, Gao DM, et al. Establishment of a metastatic model of human hepatocellular carcinoma in nude mice via orthotopic implantation of histologically intact tissues. Int. J. Cancer. 1996;66:239–243
  14. Tian J, Tang ZY, Ye SL, Liu YK, Lin ZY, Chen J, et al. New human hepatocellular carcinoma (HCC) cell line with highly metastatic potential (MHCC97) and its expressions of the factors associated with metastasis. Brit. J. Cancer. 1999;81:814–821
  15. Li Y, Tang ZY, Ye SL, Liu YK, Chen J, Xue Q, et al. Establishment of cell clones with different metastatic potential from the metastatic hepatocellular carcinoma cell line MHCC97. World J. Gastroenterol. 2001;7:630–636
  16. Deregibus MC, Cantaluppi V, Doublier S, Brizzi MF, Deambrosis I, Albini A, et al. HIV-1-Tat protein activates phosphatidylinositol 3-kinase/ AKT-dependent survival pathways in Kaposi’s sarcoma cells. J. Biol. Chem. 2002;277:25195–25202
  17. Uehara H, Kim SJ, Karashima T, Shepherd DL, Fan D, Tsan R, et al. Effects of blocking platelet-derived growth factor-receptor signaling in a mouse model of experimental prostate cancer bone metastases. J. Natl. Cancer Inst. 2003;95:458–470
  18. Kim SJ, Uehara H, Yazici S, Langley RR, He J, Tsan R, et al. Simultaneous blockade of platelet-derived growth factor-receptor and epidermal growth factor-receptor signaling and systemic administration of paclitaxel as therapy for human prostate cancer metastasis in bone of nude mice. Cancer Res. 2004;64:4201–4208
  19. Contag CH, Bachmann MH. Molecular medicine: the writing is on the vessel wall. Nature. 2004;429:618–619
  20. Langley RR, Fan D, Tsan RZ, Rebhun R, He J, Kim SJ, et al. Activation of the platelet-derived growth factor-receptor enhances survival of murine bone endothelial cells. Cancer Res. 2004;64:3727–3730
  21. Yokoi K, Sasaki T, Bucana CD, Fan D, Baker CH, Kitadai Y, et al. Simultaneous inhibition of EGFR, VEGFR, and platelet-derived growth factor receptor signaling combined with gemcitabine produces therapy of human pancreatic carcinoma and prolongs survival in an orthotopic nude mouse model. Cancer Res. 2005;65:10371–10380
  22. Kaiser WJ, Kaufman JL, Offermann MK. IFN-alpha sensitizes human umbilical vein endothelial cells to apoptosis induced by double-stranded RNA. J. Immunol. 2004;172:1699–1710
  23. Solorzano CC, Hwang R, Baker CH, Bucana CD, Pisters PW, Evans DB, et al. Administration of optimal biological dose and schedule of interferon alpha combined with gemcitabine induces apoptosis in tumor-associated endothelial cells and reduces growth of human pancreatic carcinoma implanted orthotopically in nude mice. Clin. Cancer Res. 2003;9:1858–1867
  24. Saunders WB, Bohnsack BL, Faske JB, Anthis NJ, Bayless KJ, Hirschi KK, et al. Coregulation of vascular tube stabilization by endothelial cell TIMP-2 and pericyte TIMP-3. J. Cell Biol. 2006;175:179–191
  25. Jain RK. Molecular regulation of vessel maturation. Nat. Med. 2003;9:685–693
  26. Gorog P, Pearson JD. Surface determinants of low density lipoprotein uptake by endothelial cells. Atherosclerosis. 1984;53:21–29
  27. Smalley DM, Lin JH, Curtis ML, Kobari Y, Stemerman MB, Pritchard KA. Native LDL increases endothelial cell adhesiveness by inducing intercellular adhesion molecule-1. Arterioscler. Thromb. Vasc. Biol. 1996;16:585–590
  28. May C, Doody JF, Abdullah R, Balderes P, Xu X, Chen CP, et al. Identification of a transiently exposed VE-cadherin epitope that allows for specific targeting of an antibody to the tumor neovasculature. Blood. 2005;105:4337–4344
  29. Navarro P, Ruco L, Dejana E. Differential localization of VE- and N-cadherins in human endothelial cells: VE-cadherin competes with N-cadherin for junctional localization. J. Cell Biol. 1998;140:1475–1484
  30. Menon C, Ghartey A, Canter R, Feldman M, Fraker DL. Tumor necrosis factor-alpha damages tumor blood vessel integrity by targeting VE-cadherin. Ann. Surg. 2006;244:781–791
  31. Gavard J, Gutkind JS. VEGF controls endothelial-cell permeability by promoting the beta-arrestin-dependent endocytosis of VE-cadherin. Nat. Cell Biol. 2006;8:1223–1234
  32. Kouklis P, Konstantoulaki M, Malik AB. VE-cadherin-induced Cdc42 signaling regulates formation of membrane protrusions in endothelial cells. J. Biol. Chem. 2003;278:16230–16236

PII: S0304-3835(09)00597-7

doi: 10.1016/j.canlet.2009.09.009

Cancer Letters
Volume 290, Issue 2 , Pages 204-210 , 28 April 2010

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