The 121-amino acid isoform of vascular endothelial growth factor (VEGF.sub.121) is linked by a flexible G4S tether to a cytotoxic molecule such as toxin gelonin or granzyme B and expressed as a soluble fusion protein. The VEGF.sub.121, fusion protein exhibits significant anti-tumor vascular-ablative effects that inhibit the growth of primary tumors and inhibit metastatic spread and vascularization of metastases. The VEGF.sub.121 fusion protein also target osteoclast precursor cells in vivo and inhibits osteoclastogenesis.