FIGURE 1.

Proposed mechanisms by which PSMA contributes to tumor growth and progression. Poly-γ-glutamated folates released from dead and dying tumor cells are hydrolyzed to folate by PSMA and can then be taken up by nearby healthy tumor cells via proton-coupled folate transporter (PCFT), folate receptor (FR), or reduced folate carrier (RFC). Once inside the cell, folate is again polyglutamated and used for polyamine synthesis, methylation reactions, and the nucleotide synthesis required for cell proliferation. Free glutamate released by this reaction may be taken up by glutamate receptor, stimulating proliferative growth pathways; however, the role of glutamate in this process, whether metabolic or signaling, is still being clarified.