Expression of prostate‐specific membrane antigen (PSMA), increases cell folate uptake and proliferation and suggests a novel role for PSMA in the uptake of the non‐polyglutamated folate, folic acid

Abstract

These findings implicate PSMA in both the metabolism of polyglutamated folates, and in the uptake of monoglutamated folates. Under conditions of LF or PF levels, PSMA gives cells expressing it a proliferative advantage.

101 Increased Cancer Cell Proliferation in Prostate Cancer Patients With High Levels of Serum Folate

“…Thus our results would support the second part of Kim's hypothesis, implying that at least in prostate cancer patients, very high serum folate concentrations may potentiate tumor proliferation (29). In the presence of limiting levels of folate in vitro (≤50 nM), PSMA expression increases cell folate uptake and proliferation (30). We therefore examined if expression of PSMA in tumors varied according to serum folate level; however our nonsignificant findings suggest PSMA expression is not regulated by folate levels and therefore it is unlikely that PSMA directly contributes in to the increased proliferation seen in the patients with high serum folate.…”

Modulation of One-Carbon Metabolism by B Vitamins: Implications for Transformation and Progression of Prostate Cancer

“…PSM' and its congeners are highly expressed in the normal prostate and in low-grade tumors retaining both FPH and neurocarboxypeptidase enzymatic activity (O'Keefe, Bacich, et al, 2001;Yao et al, 2008). As illustrated in Figure 18, and as suggested by Yao and O'Keefe, extensive expression of PSM' makes cells vulnerable to loss of folatemonoglutamates putatively causing intracellular folate deficiency (O'Keefe, Bacich, et al, 2001;Yao et al, 2008;Yao et al, 2010 …”

“…FPGS and FPH are competing enzymes. FPH activity is duplicated in the prostate specific membrane antigen (PSMA) and its splice variants (PSM') implicated in prostate cancer carcinogenesis (Yao et al, 2010) Figure 19. Methyltetrahydrofolate (CH3-THF) is a poor substrate for FPGS (Perry et al, 1983) and irreversible trapping of CH3-THF in B12 deficiency imposes both intracellular CH3-THF polyglutamate deficiency and loss of intracellular CH3-THF (Lowe et al, 1993).…”

Study on the prostate cancer-targeting mechanism of aptamer-modified nanoparticles and their potential anticancer effect in vivo

“…10 Such ligands are 5432 Wu et al recognized by PSMA on androgen-dependent PCa cell surfaces (LNCaP; 22Rv1), which later induce the cellular uptake of the ligand-decorated carriers via receptor-mediated endocytosis. 11 Several studies on gene targeting therapy have demonstrated the strength of ligand-modified vehicles, such as antibody, 12,13 peptide, 7,14 and APT, 6,15 in treating PSMApositive PCa cells and xenografts. The high transfection efficiency and enhanced therapeutic effect indicate that ligand-decorated nanocarriers are potentially targeted vectors to PSMA-positive PCa cells for gene delivery.…”