Use of Glycoproteins—Prostate-Specific Membrane Antigen and Galectin-3 as Primary Tumor Markers and Therapeutic Targets in the Management of Metastatic Prostate Cancer

SIMPLE SUMMARY: Prostate specific membrane antigen and galectins are proteins expressed on cell surface and their expression is associated with cancer growth and spread. The goal of this research was to look at the pattern of these two glycoproteins in the human prostate cancer microenvironment. Prostate specific membrane antigen and galectins-1,3 and 8 were the most frequently detected glycoproteins in various phases of this disease. Furthermore, prostate specific membrane antigen and galectin-3 expression are good indicators of tumor aggressiveness, and their combined expression can be valuable tool for prostate cancer diagnosis and treatment in future. Together, our findings reveal a tightly regulated “Prostate specific membrane antigen-galectin-pattern” that accompanies disease in prostate cancer and point to a key role for combined prostate specific membrane antigen and galectin-3 inhibitors in prostate cancer treatment along with standard chemotherapy. ABSTRACT: Galectins and prostate specific membrane antigen (PSMA) are glycoproteins that are functionally implicated in prostate cancer (CaP). We undertook this study to analyze the “PSMA-galectin pattern” of the human CaP microenvironment with the overarching goal of selecting novel-molecular targets for prognostic and therapeutic purposes. We examined CaP cells and biopsy samples representing different stages of the disease and found that PSMA, Gal-1, Gal-3, and Gal-8 are the most abundantly expressed glycoproteins. In contrast, other galectins such as Gal-2, 4–7, 9–13, were uniformly expressed at lower levels across all cell lines. However, biopsy samples showed markedly higher expression of PSMA, Gal-1 and Gal-3. Independently PSA and Gleason score at diagnosis correlated with the expression of PSMA, Gal-3. Additionally, the combined index of PSMA and Gal-3 expression positively correlated with Gleason score and was a better predictor of tumor aggressiveness. Together, our results recognize a tightly regulated “PSMA-galectin- pattern” that accompanies disease in CaP and highlight a major role for the combined PSMA and Gal-3 inhibitors along with standard chemotherapy for prostate cancer treatment. Inhibitor combination studies show enzalutamide (ENZ), 2-phosphonomethyl pentanedioic acid (2-PMPA), and GB1107 as highly cytotoxic for LNCaP and LNCaP-KD cells, while Docetaxel (DOC) + GB1107 show greater efficacy in PC-3 cells. Overall, 2-PMPA and GB1107 demonstrate synergistic cytotoxic effects with ENZ and DOC in various CaP cell lines.