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Mauceri, Helena J.; Seetharam, Saraswathy; Beckett, Michael A.; Lee, John Y.; Gupta, Vinay K.; Gately, Stephen; Stack, M. Sharon; Brown, Charles K.; Swedberg, Kirsten; Kufe, Donald W.; Weichselbaum, Ralph R.

Tumor production of angiostatin is enhanced after exposure to TNF‐α

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  • Media type: E-Article
  • Title: Tumor production of angiostatin is enhanced after exposure to TNF‐α
  • Contributor: Mauceri, Helena J.; Seetharam, Saraswathy; Beckett, Michael A.; Lee, John Y.; Gupta, Vinay K.; Gately, Stephen; Stack, M. Sharon; Brown, Charles K.; Swedberg, Kirsten; Kufe, Donald W.; Weichselbaum, Ralph R.
  • Published: Wiley, 2002
  • Published in: International Journal of Cancer, 97 (2002) 4, Seite 410-415
  • Language: English
  • DOI: 10.1002/ijc.1629
  • ISSN: 0020-7136; 1097-0215
  • Origination:
  • Footnote:
  • Description: AbstractInfection of tumors with an adenoviral vector expressing a chimeric gene composed of the CArG elements of the Egr‐1 promoter and a cDNA encoding TNF‐α (Ad.Egr‐TNF) has previously been shown to result in the production of high intratumoral levels of TNF‐α and thereby tumor regression. The antitumor effects of TNF‐α were ascribed to vascular thrombosis. We and others, have reported that inhibition of tumor vessel thrombosis using anticoagulation therapy does not abrogate the antitumor effects after TNF‐α treatment. To investigate the potential antiangiogenic effects of TNF‐α, we studied the generation of angiostatin after intratumoral injection of Ad.Egr‐TNF. We report an increase in plasma angiostatin levels both during and after treatment with Ad.Egr‐TNF that parallel tumor regression. We also report that TNF‐α enhances angiostatin production by inducing the activity of plasminogen activator and the release of MMP‐9 by tumor cells. These studies support a model in which the antiangiogenic effects of TNF‐α on the tumor microvasculature are mediated by generation of angiostatin. © 2002 Wiley‐Liss, Inc.
  • Access State: Open Access