PMID- 25306097
OWN - NLM
STAT- MEDLINE
DCOM- 20150528
LR  - 20220310
IS  - 1471-2407 (Electronic)
IS  - 1471-2407 (Linking)
VI  - 14
DP  - 2014 Oct 12
TI  - GLUT-1 expression is largely unrelated to both hypoxia and the Warburg phenotype 
      in squamous cell carcinomas of the vulva.
PG  - 760
LID - 10.1186/1471-2407-14-760 [doi]
LID - 760
AB  - BACKGROUND: Strongly increased uptake of glucose is a hallmark of solid malignant 
      tumors. This phenotype can be triggered by hypoxia-induced gene expression 
      changes or can occur independently of hypoxia as a consequence of malignant 
      transformation itself, and is often referred to as the Warburg effect. The 
      glycolytic phenotype has been associated with malignant progression and 
      resistance to radio- and chemotherapy. METHODS: We have chosen squamous cell 
      carcinomas of the vulva (SCC-V) as a representative solid tumor entity to study 
      the central players of this pathway, namely glucose transporter (GLUT)-1, 
      carbonic anhydrase (CA) IX, hexokinase (HK)-2 and pyruvate kinase (PK)-M2, and 
      have investigated their relationships to tumor microvessels (CD34, alphaSMA) and 
      proliferation (Ki67). Expression of these proteins was analyzed in 38 SCC-Vs, 5 
      vulvar dysplasias and 10 non-neoplastic squamous epithelia of the vulva using 
      multiparametric immunohistochemistry in registered serial sections (MIRSS). 
      RESULTS: Expression of GLUT-1 in invasive carcinomas was predominantly located in 
      the outer layers of the tumor cell aggregates close to the vascularized tumor 
      stroma, and only to a lesser extent colocalized with CA IX, which was repeatedly 
      found at larger diffusion distances away from microvessels. CA IX expression was 
      lower in invasive carcinomas compared to dysplasias and non-neoplastic tissue and 
      higher in recurrent vs. primary tumors. Ki67-positive proliferating cells were 
      partially colocalized with GLUT-1. However, HK-2 and PK-2--proteins centrally 
      involved in the Warburg phenotype--did not show such a correlation. CONCLUSIONS: 
      Consistent with prior studies, the pattern of GLUT-1 clearly indicated that a 
      large part of its expression is presumably unrelated to hypoxia. However, there 
      was also no association with HK-2 and PK-M2, suggesting that the functional 
      background of this expression is also independent of aerobic glycolysis. CA IX 
      may be worth consideration as a marker of biological hypoxia, as should its 
      pathophysiological consequences in SCC-V.
FAU - Mayer, Arnulf
AU  - Mayer A
AD  - Department of Radiooncology and Radiotherapy, University Medical Center, 
      Langenbeckstrasse 1, 55131 Mainz, Germany. arnmayer@uni-mainz.de.
FAU - Schmidt, Marcus
AU  - Schmidt M
FAU - Seeger, Alexander
AU  - Seeger A
FAU - Serras, Andre Franke
AU  - Serras AF
FAU - Vaupel, Peter
AU  - Vaupel P
FAU - Schmidberger, Heinz
AU  - Schmidberger H
LA  - eng
PT  - Journal Article
DEP - 20141012
PL  - England
TA  - BMC Cancer
JT  - BMC cancer
JID - 100967800
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Biomarkers)
RN  - 0 (Glucose Transporter Type 1)
RN  - EC 4.2.1.1 (CA9 protein, human)
RN  - EC 4.2.1.1 (Carbonic Anhydrase IX)
RN  - EC 4.2.1.1 (Carbonic Anhydrases)
SB  - IM
MH  - Antigens, Neoplasm/genetics/metabolism
MH  - Biomarkers
MH  - Carbonic Anhydrase IX
MH  - Carbonic Anhydrases/genetics/metabolism
MH  - Carcinoma, Squamous Cell/*metabolism/pathology
MH  - Female
MH  - Gene Expression
MH  - Glucose Transporter Type 1/genetics/*metabolism
MH  - Humans
MH  - Hypoxia/genetics/*metabolism
MH  - Microvessels
MH  - Neoplasm Recurrence, Local
MH  - *Phenotype
MH  - Vulvar Neoplasms/*metabolism/pathology
PMC - PMC4210616
EDAT- 2014/10/13 06:00
MHDA- 2015/05/29 06:00
PMCR- 2014/10/12
CRDT- 2014/10/13 06:00
PHST- 2014/03/06 00:00 [received]
PHST- 2014/10/02 00:00 [accepted]
PHST- 2014/10/13 06:00 [entrez]
PHST- 2014/10/13 06:00 [pubmed]
PHST- 2015/05/29 06:00 [medline]
PHST- 2014/10/12 00:00 [pmc-release]
AID - 1471-2407-14-760 [pii]
AID - 4944 [pii]
AID - 10.1186/1471-2407-14-760 [doi]
PST - epublish
SO  - BMC Cancer. 2014 Oct 12;14:760. doi: 10.1186/1471-2407-14-760.