Glucose transporter Glut-1 is detectable in peri-necrotic regions in many human tumor types but not normal tissues: Study using tissue microarrays.
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.
Airley
Rachel
R
Division of Pharmacy and Pharmaceutical Sciences, School of Applied Sciences, University of Huddersfield, Queensgate, Huddersfield, West Yorkshire, UK. r.airley@hud.ac.uk
Evans
Andrew
A
Mobasheri
Ali
A
Hewitt
Stephen M
SM
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
D015415:Biomarkers; D051272:Glucose Transporter Type 1
Eur J Cancer. 2001 Jan;37(2):204-9
11166147
Gynecol Oncol. 2000 Oct;79(1):33-7
11006027
Cancer Res. 1996 Mar 1;56(5):941-3
8640781
Clin Cancer Res. 2007 Apr 1;13(7):1971-8
17360973
Am J Physiol. 1996 Feb;270(2 Pt 1):G314-23
8779974
Acta Oncol. 1999;38(7):903-18
10606420
J Biol Chem. 1997 Feb 28;272(9):5555-62
9038162
Cancer. 1993 Nov 15;72(10):2979-85
8221565
Mol Membr Biol. 2001 Oct-Dec;18(4):247-56
11780753
Hepatology. 1994 Feb;19(2):540-2
8294112
Eur J Cancer. 2004 Mar;40(4):503-7
14962715
Biol Res. 2002;35(1):9-26
12125211
Clin Cancer Res. 2001 Apr;7(4):928-34
11309343
Am J Physiol. 1996 Apr;270(4 Pt 1):G541-53
8928783
J Biol Chem. 2000 Jul 21;275(29):21797-800
10823814
J Electron Microsc (Tokyo). 1996 Aug;45(4):275-84
8888584
Mol Cell Biol. 2001 May;21(10):3436-44
11313469
Oncol Rep. 2008 Dec;20(6):1561-7
19020742
Leuk Res. 1997 Jul;21(7):609-18
9301681
Cancer Res. 1996 Oct 1;56(19):4509-15
8813149
In Vitro. 1979 Sep;15(9):685-90
535913
Histol Histopathol. 1999 Jul;14(3):895-904
10425560
Anticancer Res. 1995 Nov-Dec;15(6B):2895-8
8669885
Mol Endocrinol. 2009 Mar;23(3):388-401
19106193
Am J Pathol. 2009 Apr;174(4):1544-52
19286567
Am J Kidney Dis. 1999 Jul;34(1):189-202
10401038
Oncology. 2001;60(2):162-9
11244332
Anticancer Res. 1997 Nov-Dec;17(6D):4299-304
9494524
Biochim Biophys Acta. 1985 Nov 21;821(1):63-6
2998464
Diabetes Care. 1990 Mar;13(3):228-43
2407478
Med Sci (Paris). 2004 Mar;20(3):277-9
15067572
Pathol Oncol Res. 1998;4(2):115-20
9654596
Clin Cancer Res. 2005 Apr 1;11(7):2768-73
15814659
Cancer Lett. 2003 Apr 25;193(2):225-33
12706881
Clin Cancer Res. 2008 Feb 15;14(4):1096-104
18281542
Cancer Metastasis Rev. 1994 Jun;13(2):139-68
7923547
Chemotherapy. 2007;53(4):233-56
17595539
Am J Clin Pathol. 2007 Aug;128(2):245-54
17638658
Br J Cancer. 2007 Sep 3;97(5):646-53
17687336
Cancer Res. 2007 Apr 1;67(7):3441-9
17409455
Cancer Res. 2004 Apr 1;64(7):2627-33
15059920
Semin Cell Biol. 1991 Dec;2(6):419-26
1813031
BMC Cancer. 2009 Jul 20;9:241
19619276
Mol Cancer Ther. 2008 Nov;7(11):3546-55
19001437
Br J Cancer. 2003 Oct 6;89(7):1290-7
14520462
Mod Pathol. 1998 May;11(5):437-43
9619596
Br J Cancer. 2003 Sep 1;89(5):870-6
12942120
Biochim Biophys Acta. 1974 Apr 29;355(1):77-104
4371599
Int J Mol Med. 2001 Jun;7(6):615-9
11351274
Science. 1985 Sep 6;229(4717):941-5
3839598
Histol Histopathol. 2004 Jan;19(1):325-35
14702201
Cancer. 1997 Sep 15;80(6):1046-51
9305704
Clin Oncol (R Coll Radiol). 2007 Aug;19(6):427-42
17482438
Br J Cancer. 2003 Jul 7;89(1):2-7
12838292
J Biol Chem. 2001 Mar 23;276(12):9519-25
11120745
Int J Cancer. 2003 Mar 10;104(1):85-91
12532423
Am J Clin Pathol. 2003 Nov;120(5):691-8
14608894
Curr Opin Investig Drugs. 2002 Oct;3(10):1527-32
12431031
Proc Natl Acad Sci U S A. 1996 Mar 5;93(5):1847-52
8700847
Int J Oncol. 2005 Jun;26(6):1477-84
15870859
Contrib Nephrol. 2001;(134):16-29
11665284