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Gastric Cancer
Published in: Gastric Cancer 1/2017

01-01-2017 | Original Article

Glucose transporters 1, 3, 6, and 10 are expressed in gastric cancer and glucose transporter 3 is associated with UICC stage and survival

Authors: Hans Anton Schlößer, Uta Drebber, Alexander Urbanski, Simon Haase, Christoph Baltin, Felix Berlth, Susanne Neiß, Michael von Bergwelt-Baildon, Ulrich Klaus Fetzner, Ute Warnecke-Eberz, Elfriede Bollschweiler, Arnulf Heinrich Hölscher, Stefan Paul Mönig, Hakan Alakus

Published in: Gastric Cancer | Issue 1/2017

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Abstract

Background

Due to proliferation and increased metabolism, cancer cells have high glucose requirements. The glucose uptake of cells is influenced by a group of membrane proteins denoted the glucose transporter family (Glut-1 to -12). Whereas increased expression and a negative correlation with survival have been described for Glut-1 in several types of cancer, the impact of other glucose transporters on tumor biology is widely unknown.

Methods

In this retrospective study, gastric cancer specimens of 150 patients who underwent total gastrectomy between 2005 and 2010 were stained for Glut-1, -3, -6, and -10 by immunohistochemistry. Expression of Glut-1, -3, -6, and 10 was correlated to prognosis as well as clinical and pathological parameters.

Results

Glut-1, Glut-3, Glut-6, and Glut-10 were expressed in 22.0, 66.0, 38.0, and 43.3 % of the analyzed samples. Whereas Glut-1, -6, and -10 did not show a correlation with prognosis, positive staining for Glut-3 was associated with higher UICC stage and inferior prognosis. The mean overall survival was 38.6 months for Glut-3 positive patients, as compared to 51.2 months for Glut-3 negative patients (p < 0.05). Coexpression of two or more of the analyzed glucose transporters was correlated to inferior prognosis. Glut-3 and UICC stage were significant prognostic factors in multivariate analysis.

Conclusions

All of the analyzed glucose transporters were expressed in a significant proportion of the gastric cancer samples. Glut-3 was associated with higher UICC stage and inferior prognosis. These findings are relevant to therapeutic approaches that target glucose metabolism as well as to imaging using radioactively labeled glucose.
Literature
1.
Koppenol WH, Bounds PL, Dang CV. Otto Warburg’s contributions to current concepts of cancer metabolism. Nat Rev Cancer. 2011;11:325–37.CrossRefPubMed
2.
Macheda ML, Rogers S, Best JD. Molecular and cellular regulation of glucose transporter (GLUT) proteins in cancer. J Cell Physiol. 2005;202:654–62.CrossRefPubMed
3.
Mueckler M, Thorens B. The SLC2 (GLUT) family of membrane transporters. Mol Aspects Med. 2013;34:121–38.
4.
Alakus H, Batur M, Schmidt M, Drebber U, Baldus SE, Vallböhmer D, et al. Variable 18F-fluorodeoxyglucose uptake in gastric cancer is associated with different levels of GLUT-1 expression. Nucl Med Commun. 2010;31:532–8.PubMed
5.
Meijer TWH, Schuurbiers OCJ, Kaanders JHAM, Looijen-Salamon MG, de Geus-Oei LF, Verhagen AFTM, et al. Differences in metabolism between adeno- and squamous cell non-small cell lung carcinomas: spatial distribution and prognostic value of GLUT1 and MCT4. Lung Cancer. 2012;76:316–23.CrossRefPubMed
6.
Saigusa S, Toiyama Y, Tanaka K, Okugawa Y, Fujikawa H, Matsushita K, et al. Prognostic significance of glucose transporter-1 (GLUT1) gene expression in rectal cancer after preoperative chemoradiotherapy. Surg Today. 2012;42:460–9.CrossRefPubMed
7.
Pinheiro C, Sousa B, Albergaria A, Paredes J, Dufloth R, Vieira D, et al. GLUT1 and CAIX expression profiles in breast cancer correlate with adverse prognostic factors and MCT1 overexpression. Histol Histopathol. 2011;26:1279–86.PubMed
8.
Tohma T, Okazumi S, Makino H, Cho A, Mochizuki R, Shuto K, et al. Overexpression of glucose transporter 1 in esophageal squamous cell carcinomas: a marker for poor prognosis. Dis Esophagus. 2005;18:185–9.CrossRefPubMed
9.
Kawamura T, Kusakabe T, Sugino T, Watanabe K, Fukuda T, Nashimoto A, et al. Expression of glucose transporter-1 in human gastric carcinoma: association with tumor aggressiveness, metastasis, and patient survival. Cancer. 2001;92:634–41.CrossRefPubMed
10.
Krzeslak A, Wojcik-Krowiranda K, Forma E, Jozwiak P, Romanowicz H, Bienkiewicz A, et al. Expression of GLUT1 and GLUT3 glucose transporters in endometrial and breast cancers. Pathol Oncol Res. 2012;18:721–8.CrossRefPubMedPubMedCentral
11.
Baer S, Casaubon L, Schwartz MR, Marcogliese A, Younes M. Glut3 expression in biopsy specimens of laryngeal carcinoma is associated with poor survival. Laryngoscope. 2002;112:393–6.CrossRefPubMed
12.
Younes M, Brown RW, Stephenson M, Gondo M, Cagle PT. Overexpression of Glut1 and Glut3 in stage I nonsmall cell lung carcinoma is associated with poor survival. Cancer. 1997;80:1046–51.CrossRefPubMed
13.
Younes M, Lechago LV, Somoano JR, Mosharaf M, Lechago J. Immunohistochemical detection of Glut3 in human tumors and normal tissues. Anticancer Res. 1997;17:2747–50.
14.
Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJH, Nicolson M, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006;355:11–20.CrossRefPubMed
15.
Kobayashi M, Kaida H, Kawahara A, Hattori S, Kurata S, Hayakawa M, et al. The relationship between GLUT-1 and vascular endothelial growth factor expression and 18F-FDG uptake in esophageal squamous cell cancer patients. Clin Nucl Med. 2012;37:447–52.CrossRefPubMed
16.
Vasseur S, Afzal S, Tardivel-Lacombe J, Park DS, Iovanna JL, Mak TW. DJ-1/PARK7 is an important mediator of hypoxia-induced cellular responses. Proc Natl Acad Sci USA. 2009;106:1111–6.CrossRefPubMedPubMedCentral
17.
18.
Wigfield SM, Winter SC, Giatromanolaki A, Taylor J, Koukourakis ML, Harris AL. PDK-1 regulates lactate production in hypoxia and is associated with poor prognosis in head and neck squamous cancer. Br J Cancer. 2008;98:1975–84.CrossRefPubMedPubMedCentral
19.
Baumunk D, Reichelt U, Hildebrandt J, Krause H, Ebbing J, Cash H, et al. Expression parameters of the metabolic pathway genes pyruvate dehydrogenase kinase-1 (PDK-1) and DJ-1/PARK7 in renal cell carcinoma (RCC). World J Urol. 2013;31:1191–6.CrossRefPubMed
20.
Hur H, Xuan Y, Kim YB, Lee G, Shim W, Yun J, et al. Expression of pyruvate dehydrogenase kinase-1 in gastric cancer as a potential therapeutic target. Int J Oncol. 2013;42:44–54.PubMed
21.
Chan DA, Sutphin PD, Nguyen P, Turcotte S, Lai EW, Banh A, et al. Targeting GLUT1 and the Warburg effect in renal cell carcinoma by chemical synthetic lethality. Sci Transl Med. 2011;3:94ra70.PubMedPubMedCentral
22.
Shen Y-M, Arbman G, Olsson B, Sun X-F. Overexpression of GLUT1 in colorectal cancer is independently associated with poor prognosis. Int J Biol Mark. 2011;26:166–72.CrossRef
23.
Eckert AW, Kappler M, Schubert J, Taubert H. Correlation of expression of hypoxia-related proteins with prognosis in oral squamous cell carcinoma patients. Oral Maxillofac Surg. 2012;16:189–96.CrossRefPubMed
24.
Sasaki H, Shitara M, Yokota K, Hikosaka Y, Moriyama S, Yano M, et al. Overexpression of GLUT1 correlates with Kras mutations in lung carcinomas. Mol Med Rep. 2012;5:599–602.PubMed
25.
Griffiths EA, Pritchard SA, McGrath SM, Valentine HR, Price PM, Welch IM, et al. Hypoxia-associated markers in gastric carcinogenesis and HIF-2alpha in gastric and gastro-oesophageal cancer prognosis. Br J Cancer. 2008;98:965–73.CrossRefPubMedPubMedCentral
26.
Wood IS, Trayhurn P. Glucose transporters (GLUT and SGLT): expanded families of sugar transport proteins. Br J Nutr. 2003;89:3–9.CrossRefPubMed
27.
Simpson IA, Dwyer D, Malide D, Moley KH, Travis A, Vannucci SJ. The facilitative glucose transporter GLUT3: 20 years of distinction. Am J Physiol Endocrinol Metab. 2008;295:E242–53.CrossRefPubMedPubMedCentral
28.
Schönberger J, Rüschoff J, Grimm D, Marienhagen J, Rümmele P, Meyringer R, et al. Glucose transporter 1 gene expression is related to thyroid neoplasms with an unfavorable prognosis: an immunohistochemical study. Thyroid. 2002;12:747–54.CrossRefPubMed
29.
Ayala FRR, Rocha RM, Carvalho KC, Carvalho AL, da Cunha IW, Lourenço SV, et al. GLUT1 and GLUT3 as potential prognostic markers for oral squamous cell carcinoma. Molecules. 2010;15:2374–87.
30.
Sawayama H, Ishimoto T, Watanabe M, Yoshida N, Baba Y, Sugihara H, et al. High expression of glucose transporter 1 on primary lesions of esophageal squamous cell carcinoma is associated with hematogenous recurrence. Ann Surg Oncol. 2014;21:1756–62.CrossRefPubMed
31.
Godoy A, Ulloa V, Rodríguez F, Reinicke K, Yañez AJ, García MDLA, et al. Differential subcellular distribution of glucose transporters GLUT1-6 and GLUT9 in human cancer: ultrastructural localization of GLUT1 and GLUT5 in breast tumor tissues. J Cell Physiol. 2006;207:614–27.
32.
de Geus-Oei L-F, van Krieken JHJM, Aliredjo RP, Krabbe PFM, Frielink C, Verhagen AFT, et al. Biological correlates of FDG uptake in non-small cell lung cancer. Lung Cancer. 2007;55:79–87.CrossRefPubMed
Metadata
Title
Glucose transporters 1, 3, 6, and 10 are expressed in gastric cancer and glucose transporter 3 is associated with UICC stage and survival
Authors
Hans Anton Schlößer
Uta Drebber
Alexander Urbanski
Simon Haase
Christoph Baltin
Felix Berlth
Susanne Neiß
Michael von Bergwelt-Baildon
Ulrich Klaus Fetzner
Ute Warnecke-Eberz
Elfriede Bollschweiler
Arnulf Heinrich Hölscher
Stefan Paul Mönig
Hakan Alakus
Publication date
01-01-2017
Publisher
Springer Japan
Published in
Gastric Cancer / Issue 1/2017
Print ISSN: 1436-3291
Electronic ISSN: 1436-3305
DOI
https://doi.org/10.1007/s10120-015-0577-x

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