PMID- 23429996
OWN - NLM
STAT- MEDLINE
DCOM- 20131031
LR  - 20230919
IS  - 1432-0533 (Electronic)
IS  - 0001-6322 (Print)
IS  - 0001-6322 (Linking)
VI  - 125
IP  - 5
DP  - 2013 May
TI  - EGFR wild-type amplification and activation promote invasion and development of 
      glioblastoma independent of angiogenesis.
PG  - 683-98
LID - 10.1007/s00401-013-1101-1 [doi]
AB  - Angiogenesis is regarded as a hallmark of cancer progression and it has been 
      postulated that solid tumor growth depends on angiogenesis. At present, however, 
      it is clear that tumor cell invasion can occur without angiogenesis, a phenomenon 
      that is particularly evident by the infiltrative growth of malignant brain 
      tumors, such as glioblastomas (GBMs). In these tumors, amplification or 
      overexpression of wild-type (wt) or truncated and constitutively activated 
      epidermal growth factor receptor (EGFR) are regarded as important events in GBM 
      development, where the complex downstream signaling events have been implicated 
      in tumor cell invasion, angiogenesis and proliferation. Here, we show that 
      amplification and in particular activation of wild-type EGFR represents an 
      underlying mechanism for non-angiogenic, invasive tumor growth. Using a 
      clinically relevant human GBM xenograft model, we show that tumor cells with EGFR 
      gene amplification and activation diffusely infiltrate normal brain tissue 
      independent of angiogenesis and that transient inhibition of EGFR activity by 
      cetuximab inhibits the invasive tumor growth. Moreover, stable, long-term 
      expression of a dominant-negative EGFR leads to a mesenchymal to epithelial-like 
      transition and induction of angiogenic tumor growth. Analysis of human GBM 
      biopsies confirmed that EGFR activation correlated with invasive/non-angiogenic 
      tumor growth. In conclusion, our results indicate that activation of wild-type 
      EGFR promotes invasion and glioblastoma development independent of angiogenesis, 
      whereas loss of its activity results in angiogenic tumor growth.
FAU - Talasila, Krishna M
AU  - Talasila KM
AD  - Department of Biomedicine, University of Bergen, Jonas Lies vei 91, 5009, Bergen, 
      Norway.
FAU - Soentgerath, Anke
AU  - Soentgerath A
FAU - Euskirchen, Philipp
AU  - Euskirchen P
FAU - Rosland, Gro V
AU  - Rosland GV
FAU - Wang, Jian
AU  - Wang J
FAU - Huszthy, Peter C
AU  - Huszthy PC
FAU - Prestegarden, Lars
AU  - Prestegarden L
FAU - Skaftnesmo, Kai Ove
AU  - Skaftnesmo KO
FAU - Sakariassen, Per Oystein
AU  - Sakariassen PO
FAU - Eskilsson, Eskil
AU  - Eskilsson E
FAU - Stieber, Daniel
AU  - Stieber D
FAU - Keunen, Olivier
AU  - Keunen O
FAU - Brekka, Narve
AU  - Brekka N
FAU - Moen, Ingrid
AU  - Moen I
FAU - Nigro, Janice M
AU  - Nigro JM
FAU - Vintermyr, Olav K
AU  - Vintermyr OK
FAU - Lund-Johansen, Morten
AU  - Lund-Johansen M
FAU - Niclou, Simone
AU  - Niclou S
FAU - Mork, Sverre J
AU  - Mork SJ
FAU - Enger, Per Oyvind
AU  - Enger PO
FAU - Bjerkvig, Rolf
AU  - Bjerkvig R
FAU - Miletic, Hrvoje
AU  - Miletic H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130222
PL  - Germany
TA  - Acta Neuropathol
JT  - Acta neuropathologica
JID - 0412041
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antineoplastic Agents)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - PQX0D8J21J (Cetuximab)
SB  - IM
MH  - Antibodies, Monoclonal, Humanized/pharmacology
MH  - Antineoplastic Agents/pharmacology
MH  - Brain Neoplasms/*genetics/*pathology
MH  - Cell Culture Techniques
MH  - Cell Line, Tumor
MH  - Cetuximab
MH  - ErbB Receptors/drug effects/genetics
MH  - Gene Amplification
MH  - Genes, erbB-1/*genetics
MH  - Glioblastoma/*genetics/*pathology
MH  - Humans
MH  - Neoplasm Invasiveness/genetics
MH  - Neovascularization, Pathologic
MH  - *Transcriptional Activation
MH  - Xenograft Model Antitumor Assays
PMC - PMC3631314
EDAT- 2013/02/23 06:00
MHDA- 2013/11/01 06:00
PMCR- 2013/02/22
CRDT- 2013/02/23 06:00
PHST- 2012/07/23 00:00 [received]
PHST- 2013/02/09 00:00 [accepted]
PHST- 2013/01/24 00:00 [revised]
PHST- 2013/02/23 06:00 [entrez]
PHST- 2013/02/23 06:00 [pubmed]
PHST- 2013/11/01 06:00 [medline]
PHST- 2013/02/22 00:00 [pmc-release]
AID - 1101 [pii]
AID - 10.1007/s00401-013-1101-1 [doi]
PST - ppublish
SO  - Acta Neuropathol. 2013 May;125(5):683-98. doi: 10.1007/s00401-013-1101-1. Epub 
      2013 Feb 22.