title: Functional expression of sodium-glucose transporters in cancer.
abstract: Glucose is a major metabolic substrate required for cancer cell survival and growth. It is mainly imported into cells by facilitated glucose transporters (GLUTs). Here we demonstrate the importance of another glucose import system, the sodium-dependent glucose transporters (SGLTs), in pancreatic and prostate adenocarcinomas, and investigate their role in cancer cell survival. Three experimental approaches were used: (i) immunohistochemical mapping of SGLT1 and SGLT2 distribution in tumors; (ii) measurement of glucose uptake in fresh isolated tumors using an SGLT-specific radioactive glucose analog, α-methyl-4-deoxy-4-[(18)F]fluoro-D-glucopyranoside (Me4FDG), which is not transported by GLUTs; and (iii) measurement of in vivo SGLT activity in mouse models of pancreatic and prostate cancer using Me4FDG-PET imaging. We found that SGLT2 is functionally expressed in pancreatic and prostate adenocarcinomas, and provide evidence that SGLT2 inhibitors block glucose uptake and reduce tumor growth and survival in a xenograft model of pancreatic cancer. We suggest that Me4FDG-PET imaging may be used to diagnose and stage pancreatic and prostate cancers, and that SGLT2 inhibitors, currently in use for treating diabetes, may be useful for cancer therapy.
authors.affiliation: Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095-6948;
authors.forename: Claudio
authors.initials: C
authors.lastname: Scafoglio
authors.affiliation: Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095-1751;
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Hirayama
authors.affiliation: Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095-6948;
authors.forename: Vladimir
authors.initials: V
authors.lastname: Kepe
authors.affiliation: Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095-6948;
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095-1751;
authors.forename: Chiara
authors.initials: C
authors.lastname: Ghezzi
authors.affiliation: Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095-6948;
authors.forename: Nagichettiar
authors.initials: N
authors.lastname: Satyamurthy
authors.affiliation: Department of Pathology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095;
authors.forename: Neda A
authors.initials: NA
authors.lastname: Moatamed
authors.affiliation: Department of Pathology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095;
authors.forename: Jiaoti
authors.initials: J
authors.lastname: Huang
authors.affiliation: Institute for Anatomy and Cell Biology, University of Würzburg, 97070 Würzburg, Germany.
authors.forename: Hermann
authors.initials: H
authors.lastname: Koepsell
authors.affiliation: Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095-6948; jbarrio@mednet.ucla.edu ewright@mednet.ucla.edu.
authors.forename: Jorge R
authors.initials: JR
authors.lastname: Barrio
authors.affiliation: Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095-1751; jbarrio@mednet.ucla.edu ewright@mednet.ucla.edu.
authors.forename: Ernest M
authors.initials: EM
authors.lastname: Wright
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D005260:Female; D005462:Fluorine Radioisotopes / Q000737:chemistry; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D051246:Glucose Transport Proteins, Facilitative / Q000378:metabolism; D005960:Glucosides / Q000737:chemistry; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism; D008297:Male; D051379:Mice; D009336:Necrosis; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D049268:Positron-Emission Tomography; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D051297:Sodium-Glucose Transporter 2 / Q000378:metabolism*; D000077203:Sodium-Glucose Transporter 2 Inhibitors
chemical_list: D005462:Fluorine Radioisotopes; D051246:Glucose Transport Proteins, Facilitative; D005960:Glucosides; C089180:SLC5A2 protein, human; C490299:Slc5a2 protein, mouse; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; C554684:methyl-4-fluoro-4-deoxyglucose
keywords: SGLT2; SGLT2-inhibitors; pancreatic cancer; prostate cancer