Correlation Between PSMA and VEGF Expression as Markers for LNCaP Tumor Angiogenesis

Abstract

Our aim is the identification and correlation of changes in tumor-associated protein expression which results from therapy. LNCaP tumors, excised from nude mice treated either by orchiectomy or with the chemotherapeutic agent paclitaxel, were evaluated for the expression of proteins and receptors associated with growth, differentiation, and angiogenesis using immunohistologic procedures. Compared to untreated control tumors, both treatments reduced the expression of vascular endothelial growth factor (VEGF), prostate-specific membrane antigen (PSMA), prostate-specific antigen (PSA), androgen receptor (AR), and epidermal growth factor receptor (EGFR). The effect of paclitaxel treatment on AR expression was the most significant (P = .005). Of particular interest was identifying a significant correlation (P < .000801) between PSMA and VEGF expression regardless of treatment modality. These altered expressions suggest that PSMA may also be a marker for angiogenesis and could represent a target for deliverable agents recognizing either prostatic tumors or endothelial development. Cell surface PSMA would then present a unique target for treatment of patients early in their development of prostatic metastases.

Prostate-Specific Membrane Antigen Protein Expression in Tumor Tissue and Risk of Lethal Prostate Cancer

“…This is consistent with the prior observation of PSMA being expressed in the endothelial cells of certain solid tumor neovasculature, including prostate cancer, renal cell carcinoma, transitional cell carcinoma of the bladder, gastric cancer, and colorectal cancer (27–30). Also, a small study of LNCaP tumors grown in nude mice found a strong positive correlation between protein expression of PSMA and vascular endothelial growth factor, a signal protein that stimulates angiogenesis (40). …”

123I-MIP-1072, a Small-Molecule Inhibitor of Prostate-Specific Membrane Antigen, Is Effective at Monitoring Tumor Response to Taxane Therapy

“…Several reports have indicated that PSMA expression, as opposed to other prostate-specific markers, is unchanged after taxane therapy in humans (32,33). For example, Kuroda et al found that androgen receptor and PSA levels were downregulated in a dose-dependent manner in response to docetaxel (33), possibly accounting for the higher PSA response rates (45%-50%) relative to the measurable response rates (8%-17%) in the 2 phase III trials that led the Food and Drug Administration to approve docetaxel in the treatment of prostate cancer (25,26).…”

Expression of Prostate-Specific Membrane Antigen (PSMA) in Brain Glioma and its Correlation with Tumor Grade

“…It is anchored to the cell membrane, which makes it an ideal promising therapeutic target (6,14). In addition, it can be internalized making it an appropriate candidate for pro-drug activity (6,14,22). In-vivo, anti-PSMA antibody has been used successfully against the neo-vasculature of a number of solid non-prostate tumors (6,23,24).…”

“…The VEGF is another angiogenic factor released by many tumor cells (22). Hypoxia promotes VEGF secretion (6) and VEGF simulates angiogenesis resulting in increased vascularity (22).…”