Role of Glutamate and Effect of Its Blockade in Prostate Cancer

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Glutamate plays a role in oncogenic metabolic and signaling pathways. In a recently reported study, Koochekpour and colleagues from the Roswell Park Cancer Institute in Buffalo, NY, investigated potential correlations of glutamate levels with prostate cancer in patients with primary or castrate-resistant metastatic disease.

Univariate and multivariate analyses showed that serum glutamate levels were significantly higher in primary prostate tumors with Gleason score ≥ 8 than in those with Gleason score ≤ 7, and higher in African Americans—who have a higher mortality rate from prostate cancer—than in Caucasian Americans. Overall, patients with metastatic disease had normal serum glutamate levels, but those with primary prostate cancer had significantly higher levels compared with healthy controls.

African Americans with metastatic disease had significantly higher serum glutamate levels than those with primary prostate cancer or benign prostate. In Caucasian Americans, serum glutamate levels were similar in normal subjects and in patients with metastatic disease.

Immunohistochemistry analysis showed weak or no expression of metabotropic glutamate receptor 1 (GRM1) in luminal acinar epithelial cells of normal or hyperplastic glands, but high expression in primary and metastatic cancer tissues. Glutamate deprivation or blockade with a glutamate receptor antagonist significantly decreased growth, migration, and invasion and induced apoptosis in both androgen-dependent and androgen-independent cancer cells.

As stated by the investigators, their findings suggest that “Glutamate expression is mechanistically associated with and may provide a biomarker of prostate cancer aggressiveness.” ■

Koochekpour S, et al: Clin Cancer Res 18:5888-5901, 2012.




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