Beta-35 is a transferrin-derived inhibitor of angiogenesis and tumor growth

An angiogenesis inhibitor named Beta-35 has been identified and purified from the conditioned medium of mouse pancreatic β cells tumor cells. Beta-35 has a molecular weight of 35 kDa and inhibits DNA synthesis of bovine capillary endothelial cells at a half-maximal concentration of approximately 5 nM. It shows anti-angiogenic activity in the chick embryo chorioallantoic membrane at a dose of about 1 μg/embryo. Amino acid microsequencing and mass spectrometric analysis of the purified protein demonstrate that Beta-35 contains the first 314 residues of the N-terminal sequence of bovine transferrin. We have cloned and expressed this protein in Escherichia coli using the corresponding gene segment of Beta-35 contained in the cDNA of human transferrin. The recombinant protein of Beta-35 shows significant anti-tumor activity at a dose of 5 mg/kg/day against human pancreatic cancer or melanoma implanted subcutaneously in SCID mice.