Differential subcellular distribution of glucose transporters GLUT1–6 and GLUT9 in human cancer: Ultrastructural localization of GLUT1 and GLUT5 in breast tumor tissues

Abstract

It has been proposed that the enhanced metabolic activity of tumor cells is accompanied by an increased expression of facilitative hexose transporters (GLUTs). However, a previous immunohistochemical analysis of GLUT1 expression in 154 malignant human neoplasms failed to detect the GLUT1 isoform in 87 tumors. We used 146 normal human tissues and 215 tumor samples to reassess GLUT1 expression. A similar number of samples were used to compare the expression of GLUT2-6 and 9. The classical expression of GLUT1-5 in different normal human tissues was confirmed, however, we were unable to detect GLUT2 in human pancreatic islet cells. GLUT6 was principally detected in testis germinal cells and GLUT9 was localized in kidney, liver, heart, and adrenal. In tumor samples, GLUT1, 2, and 5 were the main transporters detected. GLUT1 was the most widely expressed transporter, however, 42% of the samples had very low-to-negative expression levels. GLUT2 was detected in 31% of the samples, being mainly expressed in breast, colon, and liver carcinoma. GLUT5 was detected in 27% of breast and colon adenocarcinoma, liver carcinoma, lymphomas, and testis seminoma samples. In situ RT-PCR and ultrastructural immunohistochemistry confirmed GLUT5 expression in breast cancer. GLUT6 and 9 are not clearly over-expressed in human cancer. The extensive expression of GLUT2 and 5 (glucose/fructose and fructose transporters, respectively) in malignant human tissues indicates that fructose may be a good energy substrate in tumor cells. Our functional data obtained in vitro in different tumor cells support this hypothesis. Additionally, these results suggest that fructose uptake could be used for positron emission tomography imaging and, may possibly represent a novel target for the development of therapeutic agents in different human cancers.

Immunohistochemical detection of GLUT-1 can discriminate between reactive mesothelium and malignant mesothelioma

“…32,33 High GLUT-1 expression correlates with increased metabolism and glucose utilization in a number of normal tissues, and this transporter is overexpressed in a variety of human tumors. 15,16 Increased expression of GLUT-1 is also seen in conditions that induce greater dependency on glycolysis as an energy source, such as ischemia, hypoxia, or both. 34 These data suggest that overexpression of GLUT-1 may play an important role in the survival of tumor cells by maintaining an adequate energy supply to support their high metabolism and rapid growth in an often less-thanideal physiological environment.…”

“…35 GLUT-1 expression has been revealed in a variety of carcinomas, such as those of the breast, head and neck, bladder, and renal cells. [15][16][17][18][19]23 In the lung, about 34.3-100% of lung adenocarcinomas 16,[20][21][22]24 and 100% of lung squamous cell carcinomas [20][21][22]24 are reported to express GLUT-1 at the primary site. With regard to MPM, only one article has describe that two of four studied cases were positive for GLUT-1.…”

“…14 GLUT-1 is not detectable in a large proportion of cells from normal tissues and benign lesions, except for erythrocytes, germinal cells of the testis, renal tubules, perineurium of peripheral nerves, endothelial cells in blood-brain barrier vessels, and placenta (trophoblasts and capillaries). 15,16 In contrast, GLUT-1 is expressed in a variety of carcinomas such as those of the breast, head and neck, bladder, renal cells, and lung. [15][16][17][18][19][20][21][22][23][24] Previous reports suggest that the expression of GLUT-1 may be a potential marker for malignancy.…”

“…25,26 Although a few studies have demonstrated that GLUT-1 is useful for distinguishing RM from metastatic adenocarcinoma in body cavity effusions, 27-29 the study cohorts did not include MPM. Using immunohistochemistry, Godoy et al 16 analyzed coexpression of GLUT-1 and other GLUT isoforms (GLUT-2 to -6 and GLUT-9) in a variety of benign and malignant tumors, and demonstrated that two of four MPMs were positive for GLUT-1. However, they did not analyze reactive and normal mesothelium.…”

Lentiviral Vector-Mediated shRNA against AIMP2-DX2 Suppresses Lung Cancer Cell Growth through Blocking Glucose Uptake

“…Kalsi et al (2008) reported the expression of Glut-2 and Glut-4 in the human lung adenocarcinoma epithelial cell line. These proteins are also overexpressed in various tumor cells (Godoy et al, 2006). Presently, sh-DX2 decreased Glut-1, Glut-2 and Glut-4 expression in lung cancer cells.…”