THE BASIC RESIDUES OF PLACENTA GROWTH-FACTOR TYPE-2 RETRIEVE SEQUESTERED ANGIOGENIC FACTORS INTO A SOLUBLE FORM - IMPLICATIONS FOR TUMOR ANGIOGENESIS

Placenta growth factor type 1 (PlGF-1) can be synthesized by neoplasti c cells in an alternative form (PlGF-2) by the addition of basic amino acids to its classic sequence. Here we show that the basic residues o f PlGF-2 compete for the binding of basic fibroblast growth factor (bF GF) and vascular endothelial growth factor (VEGF) to heparan sulfate p roteoglycans of the cell surface and extracellular matrix. In doing so , PlGF-2 basic sequences inhibit the sequestering of VEGF and bFGF and maintain them in a highly diffusible form, thus enhancing their angio genic effect. In agreement with these in vitro data, the presence of P lGF-2 transcripts in tumors correlates with their blood vessel number. These results suggest a mechanism by which growth factor isoforms pro duced by neoplastic cells enhance the formation of new blood vessels s upporting tumor growth and progression.