Abramovitch, R., Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel
Dafni, H., Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel
Neeman, M., Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel
Nagler, A., Dept. of Bone Marrow Transplantation, Hadassah University Hospital, Jerusalem 91120, Israel
Pines, M., Institute of Animal Science, Agricultural Research Organization, Volcani Center, Bet Dagan 50250, Israel

Halofuginone, an inhibitor of collagen α1(l) gene expression was used for the treatment of subcutaneously implanted C6 glioma tumors. Halofuginone had no effect on the growth of C6 glioma spheroids in vitro, and these spheroids showed no collagen α1(l) expression and no collagen synthesis. However, a significant attenuation of tumor growth was observed in vivo, for spheroids implanted in CD-1 nude mice which were treated by oral or intraperitoneal (4 μg every 48 hours) administration of halofuginone. In these mice, treatment was associated with a dose-dependent reduction in collagen α1(l) expression and dose- and time-dependent inhibition of angiogenesis, as measured by MRI. Moreover, halofuginone treatment was associated with improved re-epithelialization of the chronic wounds that are associated with this experimental model. Oral administration of halofuginone was effective also in intervention in tumor growth, and here, too, the treatment was associated with reduced angiogenic activity and vessel regression. These results demonstrate the important role of collagen type I in tumor angiogenesis and tumor growth and implicate its role in chronic wounds. Inhibition of the expression of collagen type I provides an attractive new target for cancer therapy.