COPPER CHELATION INHIBITS TUMOR ANGIOGENESIS IN THE EXPERIMENTAL 9L GLIOSARCOMA MODEL

TO INVESTIGATE THE effects of copper (Cu)-depletion diet and D-penicil lamine treatment (CDPT) on both tumor growth and angiogenesis, we stud ied Fischer-344 rats in which 9L gliosarcoma cells had been subcutaneo usly implanted. We focused primarily on the alteration of Cu contents and the vascular density. Compared with the normal diet group, the CDP T group showed a significant reduction of tumor weight and a decrease in Cu concentration. Furthermore, the CDPT group demonstrated smaller blood vessels with significantly lower vascular density. This decrease of tumor growth was achieved by angiosuppression. Our study indicated that CDPT selectively caused Cu chelation from the tumor tissue; the normal brain tissue did not show lower Cu concentration after the trea tment. The prevention of tumor angiogenesis by this method may be very useful in cancer therapy and may help elucidate the microenvironmenta l mechanisms for cancer cells.