Decreased [18F]fluoro-2-deoxy-d-glucose incorporation and increased glucose transport are associated with resistance to 5FU in MCF7 cells in vitro

Timothy Andrew Davies Smith, Rituka I. Sharma, Weiguang G. Wang, Andrew Welch, Lutz Frank Schweiger, Elaina Susan Renata Collie-Duguid

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10 Citations (Scopus)

Abstract

Introduction: Tumor refractoriness to chemotherapy is frequently due to the acquisition of resistance. Resistant cells selected by exposure to chemotherapy agents may exhibit differences in [F-18]fluoro-2-deoxy-D-glucose (FDG) incorporation, as compared with sensitive cells.

Methods: FDG incorporation, hexokinase (HK) activity, glucose transport and ATP content were determined in clones of 5-fluorouracil (5FU)-resistant MCF7 cells, established by long-term exposure to increasing 5FU concentrations, and in parental MCF7 cells.

Results: FDG incorporation was decreased in MCF7 cells resistant to 5FU; HK activity was similar in the resistant and sensitive cells, while glucose transport was increased, as compared with sensitive cells. Treatment of cells with the glucose efflux inhibitor phloretin increased FDG incorporation to similar levels in the resistant and sensitive cells. Analysis of microarray data demonstrated the expression of GLUT1, 8 and 10 transporters in MCF7 cells. GLUT8 and 10 expression was decreased in the resistant cells, while GLUT1 was only increased in cells resistant to the lowest 5FU concentration.

Conclusion: FDG incorporation in 5FU-resistant MCF7 cells is decreased, as compared with sensitive cells. Our findings also suggest that this may be due to high rates of membrane glucose transport in the resistant cells resulting in enhanced efflux of FDG. We believe that this is the first demonstration that facilitative glucose transporters can actually decrease the incorporation of FDG.

Original languageEnglish
Pages (from-to)955-960
Number of pages6
JournalNuclear Medicine and Biology
Volume34
Issue number8
Early online date19 Sep 2007
DOIs
Publication statusPublished - Nov 2007

Keywords

  • FDG
  • MCF7 cells
  • glucose transport
  • breast-cancer cells
  • 5-fluorouracil resistance
  • human erythrocytes
  • sugar-transport
  • expression
  • GLUT1
  • chemotherapy
  • synthase
  • lung

Cite this

@article{e84d4988d51b4768a1a434cff7d22a68,
title = "Decreased [18F]fluoro-2-deoxy-d-glucose incorporation and increased glucose transport are associated with resistance to 5FU in MCF7 cells in vitro",
abstract = "Introduction: Tumor refractoriness to chemotherapy is frequently due to the acquisition of resistance. Resistant cells selected by exposure to chemotherapy agents may exhibit differences in [F-18]fluoro-2-deoxy-D-glucose (FDG) incorporation, as compared with sensitive cells. Methods: FDG incorporation, hexokinase (HK) activity, glucose transport and ATP content were determined in clones of 5-fluorouracil (5FU)-resistant MCF7 cells, established by long-term exposure to increasing 5FU concentrations, and in parental MCF7 cells. Results: FDG incorporation was decreased in MCF7 cells resistant to 5FU; HK activity was similar in the resistant and sensitive cells, while glucose transport was increased, as compared with sensitive cells. Treatment of cells with the glucose efflux inhibitor phloretin increased FDG incorporation to similar levels in the resistant and sensitive cells. Analysis of microarray data demonstrated the expression of GLUT1, 8 and 10 transporters in MCF7 cells. GLUT8 and 10 expression was decreased in the resistant cells, while GLUT1 was only increased in cells resistant to the lowest 5FU concentration. Conclusion: FDG incorporation in 5FU-resistant MCF7 cells is decreased, as compared with sensitive cells. Our findings also suggest that this may be due to high rates of membrane glucose transport in the resistant cells resulting in enhanced efflux of FDG. We believe that this is the first demonstration that facilitative glucose transporters can actually decrease the incorporation of FDG.",
keywords = "FDG, MCF7 cells, glucose transport, breast-cancer cells, 5-fluorouracil resistance, human erythrocytes, sugar-transport, expression, GLUT1, chemotherapy, synthase, lung",
author = "Smith, {Timothy Andrew Davies} and Sharma, {Rituka I.} and Wang, {Weiguang G.} and Andrew Welch and Schweiger, {Lutz Frank} and Collie-Duguid, {Elaina Susan Renata}",
year = "2007",
month = "11",
doi = "10.1016/j.nucmedbio.2007.07.007",
language = "English",
volume = "34",
pages = "955--960",
journal = "Nuclear Medicine and Biology",
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TY - JOUR

T1 - Decreased [18F]fluoro-2-deoxy-d-glucose incorporation and increased glucose transport are associated with resistance to 5FU in MCF7 cells in vitro

AU - Smith, Timothy Andrew Davies

AU - Sharma, Rituka I.

AU - Wang, Weiguang G.

AU - Welch, Andrew

AU - Schweiger, Lutz Frank

AU - Collie-Duguid, Elaina Susan Renata

PY - 2007/11

Y1 - 2007/11

N2 - Introduction: Tumor refractoriness to chemotherapy is frequently due to the acquisition of resistance. Resistant cells selected by exposure to chemotherapy agents may exhibit differences in [F-18]fluoro-2-deoxy-D-glucose (FDG) incorporation, as compared with sensitive cells. Methods: FDG incorporation, hexokinase (HK) activity, glucose transport and ATP content were determined in clones of 5-fluorouracil (5FU)-resistant MCF7 cells, established by long-term exposure to increasing 5FU concentrations, and in parental MCF7 cells. Results: FDG incorporation was decreased in MCF7 cells resistant to 5FU; HK activity was similar in the resistant and sensitive cells, while glucose transport was increased, as compared with sensitive cells. Treatment of cells with the glucose efflux inhibitor phloretin increased FDG incorporation to similar levels in the resistant and sensitive cells. Analysis of microarray data demonstrated the expression of GLUT1, 8 and 10 transporters in MCF7 cells. GLUT8 and 10 expression was decreased in the resistant cells, while GLUT1 was only increased in cells resistant to the lowest 5FU concentration. Conclusion: FDG incorporation in 5FU-resistant MCF7 cells is decreased, as compared with sensitive cells. Our findings also suggest that this may be due to high rates of membrane glucose transport in the resistant cells resulting in enhanced efflux of FDG. We believe that this is the first demonstration that facilitative glucose transporters can actually decrease the incorporation of FDG.

AB - Introduction: Tumor refractoriness to chemotherapy is frequently due to the acquisition of resistance. Resistant cells selected by exposure to chemotherapy agents may exhibit differences in [F-18]fluoro-2-deoxy-D-glucose (FDG) incorporation, as compared with sensitive cells. Methods: FDG incorporation, hexokinase (HK) activity, glucose transport and ATP content were determined in clones of 5-fluorouracil (5FU)-resistant MCF7 cells, established by long-term exposure to increasing 5FU concentrations, and in parental MCF7 cells. Results: FDG incorporation was decreased in MCF7 cells resistant to 5FU; HK activity was similar in the resistant and sensitive cells, while glucose transport was increased, as compared with sensitive cells. Treatment of cells with the glucose efflux inhibitor phloretin increased FDG incorporation to similar levels in the resistant and sensitive cells. Analysis of microarray data demonstrated the expression of GLUT1, 8 and 10 transporters in MCF7 cells. GLUT8 and 10 expression was decreased in the resistant cells, while GLUT1 was only increased in cells resistant to the lowest 5FU concentration. Conclusion: FDG incorporation in 5FU-resistant MCF7 cells is decreased, as compared with sensitive cells. Our findings also suggest that this may be due to high rates of membrane glucose transport in the resistant cells resulting in enhanced efflux of FDG. We believe that this is the first demonstration that facilitative glucose transporters can actually decrease the incorporation of FDG.

KW - FDG

KW - MCF7 cells

KW - glucose transport

KW - breast-cancer cells

KW - 5-fluorouracil resistance

KW - human erythrocytes

KW - sugar-transport

KW - expression

KW - GLUT1

KW - chemotherapy

KW - synthase

KW - lung

U2 - 10.1016/j.nucmedbio.2007.07.007

DO - 10.1016/j.nucmedbio.2007.07.007

M3 - Article

VL - 34

SP - 955

EP - 960

JO - Nuclear Medicine and Biology

JF - Nuclear Medicine and Biology

SN - 0969-8051

IS - 8

ER -