Copper Chelation Inhibits Tumor Angiogenesis in the Experimental 9L Gliosarcoma Model

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Abstract
TO INVESTIGATE THE effects of copper (Cu)-depletion diet and D-penicillamine treatment (CDPT) on both tumor growth and angiogenesis, we studied Fischer-344 rats in which 9L gliosarcoma cells had been subcutaneously implanted. We focused primarily on the alteration of Cu contents and the vascular density. Compared with the normal diet group, the CDPT 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 treatment. The prevention of tumor angiogenesis by this method may be very useful in cancer therapy and may help elucidate the microenvironmental mechanisms for cancer cells.