Cellular distribution of Glut‐1 and Glut‐5 in benign and malignant human prostate tissue

Abstract

Over-expression of hexose transporters (Gluts), specifically Glut-1, is a common event in human malignancies. In prostate cancer (CaP), however, expression of Gluts has been characterized poorly. In this study, expression and distribution of Glut-1 and Glut-5 proteins were characterized using immunohistochemistry in 76 specimens of benign prostate, 10 specimens of high-grade intraepithelial neoplasia (HGPIN), and 28 specimens of CaP. In addition, mRNA expression of Glut-2, Glut-7, Glut-9, and Glut-11 was analyzed in a set of five specimens of benign prostate and CaP. In benign prostate, Glut-1 localized to the basal cells and to the basolateral membrane of secretory/luminal epithelial cells. Glut-5, however, localized to the apical membrane of secretory/luminal epithelial cells. In HGPIN, Glut-1 was immunohistochemically undetectable. Glut-5, however, localized to the apical membrane of the neoplastic epithelial cells. In CaP, Glut-1 and Glut-5, were immunohistochemically undetectable. However, over-expression of GLUT1 was observed in some specimens of highly proliferative intraductal CaP. Glut-7, Glut-9, and Glut-11 mRNAs were detected in benign prostate and CaP, however, only Glut-11 mRNA was consistently up-regulated in CaP compared to benign prostate. Low levels of expression of Glut-1 protein in the majority of CaP could explain, at least in part, the limited clinical applicability of positron emission tomography using 2-[18F]-fluoro-2-deoxy-D-glucose for imaging CaP. Moreover, expression of Glut-5 in HGPIN suggested that fructose could be utilized as potential metabolic substrate in HGPIN. Understanding the molecular mechanisms involved in regulation/dysregulation of Gluts in CaP could provide insight in the understanding of hexose metabolism in CaP.

Organ-Specific Cancer Metabolism and Its Potential for Therapy

“…This is further in agreement with cell line studies, which show that the metastastic androgen-sensitive cell line LNCaP and the castration-resistant low-differentiation cell lines DU-145 and PC-3 are sensitive to glucose starvation [152] and that androgen signaling enhances the expression of glycolytic enzymes [161][162][163]. However, whether or not an increased expression of the glucose transporter 1 or other hexose transporters are causal for this phenotype is still a matter of debate, since histological data are inconclusive [164][165][166][167].…”

Incidental Abnormal FDG Uptake in the Prostate on 18-fluoro-2-Deoxyglucose Positron Emission Tomography-Computed Tomography Scans

“…In addition, GLUT-1 was undetectable in high-grade prostatic intraepithelial neoplasia and prostate cancer. These results suggest that carcinogenesis in prostate tissue is not associated with GLUT-1 expression, and therefore that glucose might not play an important role in maintaining prostate cancer cell metabolism (Reinicke et al, 2012). Consistent with this, an additional study examined resected prostate cancer tissues immunohistochemically using anti-GLUT-1 antibodies, and revealed only weak positive staining.…”

“…Furthermore, they reported that FDG accumulation was not related to clinical stage or histological grade. The study by Effert et al used continuous bladder irrigation with a Foley catheter to reduce the artifacts caused by residual urinary activity; however, this did not result in increased tumor uptake (Effert et al, 1996;Reinicke et al, 2012). This result could be explained by reports that prostate cancer uses hexoses other than glucose, such as fructose, preferentially.…”

Roles of facilitative glucose transporter GLUT1 in [18F]FDG positron emission tomography (PET) imaging of human diseases

“…[124,125]. An enhanced expression of GLUT1 is found in prostate carcinoma cells, which includes a novel co-localisation of GLUT1 with a Golgi marker.…”