title: Glucose transporter Glut-1 is detectable in peri-necrotic regions in many human tumor types but not normal tissues: Study using tissue microarrays.
abstract: The hypoxic tumor microenvironment is associated with malignant progression and poor treatment response. The glucose transporter Glut-1 is a prognostic factor and putative hypoxia marker. So far, studies of Glut-1 in cancer have utilized conventional immunohistochemical analysis in a series of individual biopsy or surgical specimens. Tissue microarrays, however, provide a rapid, inexpensive means of profiling biomarker expression. To evaluate hypoxia markers, tissue cores must show the architectural features of hypoxia; i.e. viable tissue surrounding necrotic regions. Glut-1 may be a useful biomarker to validate tissue microarrays for use in studies of hypoxia-regulated genes in cancer. In this study, we carried out immunohistochemical detection of Glut-1 protein in many tumor and normal tissue types in a range of tissue microarrays. Glut-1 was frequently found in peri-necrotic regions, occurring in 9/34 lymphomas, 6/12 melanomas, and 5/16 glioblastomas; and in 43/54 lung, 22/84 colon, and 23/60 ovarian tumors. Expression was rare in breast (6/40) and prostate (1/57) tumors, and in normal tissue, was restricted to spleen, tongue, and CNS endothelium. In conclusion, tissue microarrays enable the observation of Glut-1 expression in peri-necrotic regions, which may be linked to hypoxia, and reflect previous studies showing differential Glut-1 expression across tumor types and non-malignant tissue.
authors.affiliation: Division of Pharmacy and Pharmaceutical Sciences, School of Applied Sciences, University of Huddersfield, Queensgate, Huddersfield, West Yorkshire, UK. r.airley@hud.ac.uk
authors.forename: Rachel
authors.initials: R
authors.lastname: Airley
authors.forename: Andrew
authors.initials: A
authors.lastname: Evans
authors.forename: Ali
authors.initials: A
authors.lastname: Mobasheri
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Hewitt
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D051272:Glucose Transporter Type 1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism; D009336:Necrosis; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009928:Organ Specificity; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism; D011379:Prognosis; D040081:Protein Array Analysis; D012016:Reference Values
chemical_list: D015415:Biomarkers; D051272:Glucose Transporter Type 1
references.citation: Eur J Cancer. 2001 Jan;37(2):204-9
references.pmid: 11166147
references.citation: Gynecol Oncol. 2000 Oct;79(1):33-7
references.pmid: 11006027
references.citation: Cancer Res. 1996 Mar 1;56(5):941-3
references.pmid: 8640781
references.citation: Clin Cancer Res. 2007 Apr 1;13(7):1971-8
references.pmid: 17360973
references.citation: Am J Physiol. 1996 Feb;270(2 Pt 1):G314-23
references.pmid: 8779974
references.citation: Acta Oncol. 1999;38(7):903-18
references.pmid: 10606420
references.citation: J Biol Chem. 1997 Feb 28;272(9):5555-62
references.pmid: 9038162
references.citation: Cancer. 1993 Nov 15;72(10):2979-85
references.pmid: 8221565
references.citation: Mol Membr Biol. 2001 Oct-Dec;18(4):247-56
references.pmid: 11780753
references.citation: Hepatology. 1994 Feb;19(2):540-2
references.pmid: 8294112
references.citation: Eur J Cancer. 2004 Mar;40(4):503-7
references.pmid: 14962715
references.citation: Biol Res. 2002;35(1):9-26
references.pmid: 12125211
references.citation: Clin Cancer Res. 2001 Apr;7(4):928-34
references.pmid: 11309343
references.citation: Am J Physiol. 1996 Apr;270(4 Pt 1):G541-53
references.pmid: 8928783
references.citation: J Biol Chem. 2000 Jul 21;275(29):21797-800
references.pmid: 10823814
references.citation: J Electron Microsc (Tokyo). 1996 Aug;45(4):275-84
references.pmid: 8888584
references.citation: Mol Cell Biol. 2001 May;21(10):3436-44
references.pmid: 11313469
references.citation: Oncol Rep. 2008 Dec;20(6):1561-7
references.pmid: 19020742
references.citation: Leuk Res. 1997 Jul;21(7):609-18
references.pmid: 9301681
references.citation: Cancer Res. 1996 Oct 1;56(19):4509-15
references.pmid: 8813149
references.citation: In Vitro. 1979 Sep;15(9):685-90
references.pmid: 535913
references.citation: Histol Histopathol. 1999 Jul;14(3):895-904
references.pmid: 10425560
references.citation: Anticancer Res. 1995 Nov-Dec;15(6B):2895-8
references.pmid: 8669885
references.citation: Mol Endocrinol. 2009 Mar;23(3):388-401
references.pmid: 19106193
references.citation: Am J Pathol. 2009 Apr;174(4):1544-52
references.pmid: 19286567
references.citation: Am J Kidney Dis. 1999 Jul;34(1):189-202
references.pmid: 10401038
references.citation: Oncology. 2001;60(2):162-9
references.pmid: 11244332
references.citation: Anticancer Res. 1997 Nov-Dec;17(6D):4299-304
references.pmid: 9494524
references.citation: Biochim Biophys Acta. 1985 Nov 21;821(1):63-6
references.pmid: 2998464
references.citation: Diabetes Care. 1990 Mar;13(3):228-43
references.pmid: 2407478
references.citation: Med Sci (Paris). 2004 Mar;20(3):277-9
references.pmid: 15067572
references.citation: Pathol Oncol Res. 1998;4(2):115-20
references.pmid: 9654596
references.citation: Clin Cancer Res. 2005 Apr 1;11(7):2768-73
references.pmid: 15814659
references.citation: Cancer Lett. 2003 Apr 25;193(2):225-33
references.pmid: 12706881
references.citation: Clin Cancer Res. 2008 Feb 15;14(4):1096-104
references.pmid: 18281542
references.citation: Cancer Metastasis Rev. 1994 Jun;13(2):139-68
references.pmid: 7923547
references.citation: Chemotherapy. 2007;53(4):233-56
references.pmid: 17595539
references.citation: Am J Clin Pathol. 2007 Aug;128(2):245-54
references.pmid: 17638658
references.citation: Br J Cancer. 2007 Sep 3;97(5):646-53
references.pmid: 17687336
references.citation: Cancer Res. 2007 Apr 1;67(7):3441-9
references.pmid: 17409455
references.citation: Cancer Res. 2004 Apr 1;64(7):2627-33
references.pmid: 15059920
references.citation: Semin Cell Biol. 1991 Dec;2(6):419-26
references.pmid: 1813031
references.citation: BMC Cancer. 2009 Jul 20;9:241
references.pmid: 19619276
references.citation: Mol Cancer Ther. 2008 Nov;7(11):3546-55
references.pmid: 19001437
references.citation: Br J Cancer. 2003 Oct 6;89(7):1290-7
references.pmid: 14520462
references.citation: Mod Pathol. 1998 May;11(5):437-43
references.pmid: 9619596
references.citation: Br J Cancer. 2003 Sep 1;89(5):870-6
references.pmid: 12942120
references.citation: Biochim Biophys Acta. 1974 Apr 29;355(1):77-104
references.pmid: 4371599
references.citation: Int J Mol Med. 2001 Jun;7(6):615-9
references.pmid: 11351274
references.citation: Science. 1985 Sep 6;229(4717):941-5
references.pmid: 3839598
references.citation: Histol Histopathol. 2004 Jan;19(1):325-35
references.pmid: 14702201
references.citation: Cancer. 1997 Sep 15;80(6):1046-51
references.pmid: 9305704
references.citation: Clin Oncol (R Coll Radiol). 2007 Aug;19(6):427-42
references.pmid: 17482438
references.citation: Br J Cancer. 2003 Jul 7;89(1):2-7
references.pmid: 12838292
references.citation: J Biol Chem. 2001 Mar 23;276(12):9519-25
references.pmid: 11120745
references.citation: Int J Cancer. 2003 Mar 10;104(1):85-91
references.pmid: 12532423
references.citation: Am J Clin Pathol. 2003 Nov;120(5):691-8
references.pmid: 14608894
references.citation: Curr Opin Investig Drugs. 2002 Oct;3(10):1527-32
references.pmid: 12431031
references.citation: Proc Natl Acad Sci U S A. 1996 Mar 5;93(5):1847-52
references.pmid: 8700847
references.citation: Int J Oncol. 2005 Jun;26(6):1477-84
references.pmid: 15870859
references.citation: Contrib Nephrol. 2001;(134):16-29
references.pmid: 11665284