Work

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

Year: 2001

Type: article

Abstract: Infection 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-alpha (Ad.Egr-TNF) has previously been shown to result in the production of high intratumoral levels of TNF-alpha and thereby tumor regression. The antitumor effects of TNF-alpha 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-alpha treatment. To investigate the potential antiangiogenic effects of TNF-alpha, 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-alpha 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-alpha on the tumor microvasculature are mediated by generation of angiostatin.

Source: International Journal of Cancer

DOI: 10.1002/ijc.1629