PMID- 23712426
OWN - NLM
STAT- MEDLINE
DCOM- 20140625
LR  - 20171116
IS  - 1699-5848 (Electronic)
IS  - 0213-3911 (Linking)
VI  - 28
IP  - 12
DP  - 2013 Dec
TI  - The receptor for advanced glycation end products is dispensable in a mouse model 
      of oral and esophageal carcinogenesis.
PG  - 1585-94
LID - 10.14670/HH-28.1585 [doi]
AB  - Aberrant expression of the receptor for advanced glycation end products (RAGE) 
      and its ligands, such as S100/Calgranulins, has been demonstrated in squamous 
      cell carcinomas of the upper aerodigestive tract. However, the question whether 
      RAGE signaling is causally linked with neoplastic transformation of keratinocytes 
      in mucosal epithelia has not been addressed so far. We used the well-established 
      mouse model of 4-nitroquinoline-1-oxide (4-NQO) induced tumorigenesis to 
      investigate tumor development in control and RAGE-deficient (Rage(-/-)) animals. 
      Although 4-NQO induced lesions of the tongue and the esophagus showed strong 
      induction of the RAGE ligands S100a8 and S100a9, we did not observe any 
      significant difference in tumor incidence or multiplicity between control and 
      Rage(-/-) mice. Furthermore, detailed analysis of tumor sections by histological 
      and immunohistochemical staining revealed no difference in either the size or 
      histological architecture of dysplastic lesions, tumor cell proliferation, or the 
      number of inflammatory immune cells in the tumor microenvironment. Finally, we 
      detected induced transcript and protein levels of the Toll-like receptor 4 (Tlr4) 
      in 4-NQO induced lesions, suggesting that signaling via the S100-Tlr4 axis may 
      compensate for the lack of RAGE in early stages of tumor development. Our data 
      demonstrate that RAGE is dispensable in the onset of genotoxic induced oral and 
      esophageal squamous cell carcinoma and provide evidence for an alternative 
      pathway of S100-Calgranulin signaling via Tlr4.
FAU - Mark, Regina
AU  - Mark R
AD  - Experimental Head and Neck Oncology, Department of Otolaryngology, Head and Neck 
      Surgery, University Hospital Heidelberg, and Division of Signal Transduction and 
      Growth Control (A100), DKFZ-ZMBH Alliance, German Cancer Research Center 
      Heidelberg, Heidelberg, Germany.
FAU - Bermejo, Justo Lorenzo
AU  - Bermejo JL
FAU - Bierhaus, Angelika
AU  - Bierhaus A
FAU - Plinkert, Peter K
AU  - Plinkert PK
FAU - Angel, Peter
AU  - Angel P
FAU - Hess, Jochen
AU  - Hess J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130528
PL  - Spain
TA  - Histol Histopathol
JT  - Histology and histopathology
JID - 8609357
RN  - 0 (Receptor for Advanced Glycation End Products)
RN  - 0 (Receptors, Immunologic)
SB  - IM
MH  - Animals
MH  - Carcinogenesis/*metabolism
MH  - Carcinoma, Squamous Cell/*metabolism
MH  - Disease Models, Animal
MH  - Esophageal Neoplasms/*metabolism
MH  - Immunohistochemistry
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mouth Neoplasms/*metabolism
MH  - Receptor for Advanced Glycation End Products
MH  - Receptors, Immunologic/*metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Signal Transduction/physiology
EDAT- 2013/05/29 06:00
MHDA- 2014/06/26 06:00
CRDT- 2013/05/29 06:00
PHST- 2013/05/29 06:00 [entrez]
PHST- 2013/05/29 06:00 [pubmed]
PHST- 2014/06/26 06:00 [medline]
AID - HH-11-348 [pii]
AID - 10.14670/HH-28.1585 [doi]
PST - ppublish
SO  - Histol Histopathol. 2013 Dec;28(12):1585-94. doi: 10.14670/HH-28.1585. Epub 2013 
      May 28.