Suppression of angiogenesis and therapy of human colon cancer liver metastasis by systemic administration of interferon-alpha.

Abstract

The purpose of this study was to determine whether systemic administration of interferon-alpha (IFN-alpha) can inhibit liver metastasis produced in nude mice by human colon cancer cells. KM12L4 (IFN-alpha-sensitive) or KM12L4 IFN(R) (IFN-alpha-resistant) cells were injected into the spleen of nude mice. Seven days later, the mice were treated with subcutaneous (s.c.) injections of IFN-alpha (70,000 units/week) at different dosing schedules (1, 2, or 7 times/week). Significant inhibition of tumor growth, vascularization and expression of basic fibroblast growth factor (bFGF) or matrix metalloproteinase-9 (MMP-9) mRNA and protein occurred in mice given daily injections of IFN-alpha. Kinetic analysis of therapy showed that daily s.c. administrations of 10,000 units of IFN-alpha induced apoptosis in liver metastasis-associated endothelial cells, followed by inhibition of tumor cell division and apoptosis of tumor cells. These data suggest that the antiangiogenic activity of IFN-alpha-2a depends on frequent administration of the optimal biologic dose.

• Authors: S Ozawa, H Shinohara, H O Kanayama, C J Bruns, C D Bucana, L M Ellis, D W Davis, I J Fidler
• Journal: Neoplasia (New York, N.Y.) (Neoplasia) 2001 Mar-Apr Vol. 3 Issue 2 Pg. 154-64 ISSN: 1522-8002 [Print] United States
• PMID: 11420751 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Interferon Type I
• Interferon alpha-2
• Interferon-alpha
• Platelet Endothelial Cell Adhesion Molecule-1
• Proliferating Cell Nuclear Antigen
• RNA, Messenger
• Recombinant Proteins
• Fibroblast Growth Factor 2
• Matrix Metalloproteinase 8

Topics

• Animals
• Apoptosis
• Colonic Neoplasms (drug therapy, pathology)
• Dose-Response Relationship, Drug
• Down-Regulation
• Fibroblast Growth Factor 2 (biosynthesis)
• Humans
• Immunohistochemistry
• In Situ Hybridization
• In Situ Nick-End Labeling
• Interferon Type I (therapeutic use)
• Interferon alpha-2
• Interferon-alpha (therapeutic use)
• Kinetics
• Liver Neoplasms (blood supply, drug therapy, secondary)
• Male
• Matrix Metalloproteinase 8 (biosynthesis)
• Mice
• Mice, Nude
• Neoplasm Metastasis
• Neovascularization, Pathologic
• Platelet Endothelial Cell Adhesion Molecule-1 (biosynthesis)
• Proliferating Cell Nuclear Antigen (biosynthesis)
• RNA, Messenger (metabolism)
• Recombinant Proteins
• Spleen (metabolism)
• Time Factors
• Tumor Cells, Cultured