Differential subcellular distribution of glucose transporters GLUT1-6 and GLUT9 in human cancer: ultrastructural localization of GLUT1 and GLUT5 in breast tumor tissues.
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.
Godoy
Alejandro
A
Departamento de Biología Celular, Facultad de Ciencias Biológicas, Universidad de Concepción, Casilla 160C, Concepción, Chile.
Ulloa
Viviana
V
Rodríguez
Federico
F
Reinicke
Karin
K
Yañez
Alejandro J
AJ
García
María de los Angeles
Mde L
Medina
Rodolfo A
RA
Carrasco
Mónica
M
Barberis
Sofía
S
Castro
Tamara
T
Martínez
Fernando
F
Koch
Ximena
X
Vera
Juan Carlos
JC
Poblete
María Teresa
MT
Figueroa
Carlos D
CD
Peruzzo
Bruno
B
Pérez
Fernando
F
Nualart
Francisco
F
D000818:Animals; D001706:Biopsy; D001940:Breast / Q000378:metabolism* / Q000473:pathology* / Q000648:ultrastructure; D015972:Gene Expression Regulation, Neoplastic; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics / Q000378:metabolism*; D006262:Health; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D016253:Microscopy, Immunoelectron; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology* / Q000648:ultrastructure; D009928:Organ Specificity; D051381:Rats; D014407:Tumor Cells, Cultured
D051246:Glucose Transport Proteins, Facilitative