Clinical & Experimental Metastasis

, Volume 19, Issue 7, pp 609–615

Evidence for the causal role of endogenous interferon-α/β in the regulation of angiogenesis, tumorigenicity, and metastasis of cutaneous neoplasms

  • Marya F. McCarty
  • Diane Bielenberg
  • Cherrie Donawho
  • Corazon D. Bucana
  • Isaiah J. Fidler
Article

DOI: 10.1023/A:1020923326441

Cite this article as:
McCarty, M.F., Bielenberg, D., Donawho, C. et al. Clin Exp Metastasis (2002) 19: 609. doi:10.1023/A:1020923326441

Abstract

Primary tumor growth and metastasis depend on angiogenesis, which is determined by the balance between proangiogenic and antiangiogenic molecules. Interferon (IFN)-α and -β inhibit angiogenesis through downregulation of interleukin-8, matrix metalloproteinase-9, and basic fibroblast growth factor. To provide evidence for the causal role of IFN-α/β in the induction of neoplasms, their angiogenesis, and hence, progressive growth, we carried out experiments using 129S6 IFN-α/β receptor −/− mice back-crossed to BALB/c nude mice. Subcutaneous angiogenesis was determined following implantation of gelfoam sponges containing 0.4% agarose and several proangiogenic molecules. Tumorigenicity and production of lung metastasis were determined subsequent to subcutaneous and intravenous injections, respectively, of highly metastatic A375SM human melanoma cells. Carcinogenesis was induced by chronic exposure of mice to UVB radiation (5 kJ/m2, 3 times/week). Angiogenesis, tumorigenicity, and production of metastasis, as well as development of autochthonous skin tumors, were all accelerated in IFN-α/β receptor −/− mice as compared to control mice. Collectively, the data show that inability to respond to endogenous IFN-α/β (through a mutation in the IFN-α/β receptor) leads to increased susceptibility to carcinogenesis, enhanced angiogenesis, tumorigenicity, and metastasis.

angiogenesis carcinogenesis gelfoam sponges interferon metastasis 

Copyright information

© Kluwer Academic Publishers 2002

Authors and Affiliations

  • Marya F. McCarty
    • 1
  • Diane Bielenberg
    • 1
  • Cherrie Donawho
    • 1
  • Corazon D. Bucana
    • 1
  • Isaiah J. Fidler
    • 1
  1. 1.Department of Cancer BiologyThe University of Texas M.D. Anderson Cancer CenterHoustonUSA

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