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.