PMID- 27933395
OWN - NLM
STAT- MEDLINE
DCOM- 20170320
LR  - 20181113
IS  - 1432-1335 (Electronic)
IS  - 0171-5216 (Print)
IS  - 0171-5216 (Linking)
VI  - 143
IP  - 4
DP  - 2017 Apr
TI  - Influence of the HER receptor ligand system on sensitivity to cetuximab and 
      trastuzumab in gastric cancer cell lines.
PG  - 573-600
LID - 10.1007/s00432-016-2308-z [doi]
AB  - PURPOSE: Gastric cancer remains a major health concern, and improvement of the 
      therapeutic options is crucial. Treatment with targeted therapeutics such as the 
      EGFR-targeting antibody cetuximab or the HER2-targeting antibody trastuzumab is 
      either ineffective or moderately effective in this disease, respectively. In this 
      study, we analysed the involvement of the HER receptor ligands amphiregulin 
      (AREG), epidermal growth factor (EGF), heparin-binding epidermal growth factor 
      (HB-EGF) and transforming growth factor alpha (TGFalpha) in the responsiveness of 
      gastric cancer cell lines to cetuximab and trastuzumab. METHODS: A panel of 11 
      gastric cancer cell lines was characterized for cetuximab and trastuzumab 
      sensitivity, ligand secretion and expression and activation of the HER receptors 
      using WST-1 cell proliferation assays, ELISAs and Western blot analyses. We 
      further investigated the effects of an exogenous ligand application on the 
      cetuximab and trastuzumab sensitivity. RESULTS: We found no correlation between 
      TGFalpha secretion and the sensitivity to cetuximab or trastuzumab. For AREG, we 
      confirmed previous results indicating that this ligand is a positive predictor of 
      cetuximab sensitivity. Exogenous HB-EGF was effective in rescuing sensitive cell 
      lines from inhibition of cell proliferation by both, cetuximab and trastuzumab. 
      CONCLUSIONS: Our data indicate that HB-EGF may be a useful marker for the 
      prediction of trastuzumab sensitivity in gastric cancer.
FAU - Kneissl, Julia
AU  - Kneissl J
AD  - Institut fur Allgemeine Pathologie und Pathologische Anatomie, Technische 
      Universitat Munchen, Klinikum rechts der Isar, Trogerstr. 18, 81675, Munich, 
      Germany.
FAU - Hartmann, Anja
AU  - Hartmann A
AD  - Institut fur Allgemeine Pathologie und Pathologische Anatomie, Technische 
      Universitat Munchen, Klinikum rechts der Isar, Trogerstr. 18, 81675, Munich, 
      Germany.
FAU - Pfarr, Nicole
AU  - Pfarr N
AD  - Institut fur Allgemeine Pathologie und Pathologische Anatomie, Technische 
      Universitat Munchen, Klinikum rechts der Isar, Trogerstr. 18, 81675, Munich, 
      Germany.
FAU - Erlmeier, Franziska
AU  - Erlmeier F
AD  - Institut fur Allgemeine Pathologie und Pathologische Anatomie, Technische 
      Universitat Munchen, Klinikum rechts der Isar, Trogerstr. 18, 81675, Munich, 
      Germany.
FAU - Lorber, Thomas
AU  - Lorber T
AD  - Institute for Pathology, University Hospital Basel, Schonbeinstrasse 40, 4031, 
      Basel, Switzerland.
FAU - Keller, Simone
AU  - Keller S
AD  - Institut fur Allgemeine Pathologie und Pathologische Anatomie, Technische 
      Universitat Munchen, Klinikum rechts der Isar, Trogerstr. 18, 81675, Munich, 
      Germany.
FAU - Zwingenberger, Gwen
AU  - Zwingenberger G
AD  - Institut fur Allgemeine Pathologie und Pathologische Anatomie, Technische 
      Universitat Munchen, Klinikum rechts der Isar, Trogerstr. 18, 81675, Munich, 
      Germany.
FAU - Weichert, Wilko
AU  - Weichert W
AD  - Institut fur Allgemeine Pathologie und Pathologische Anatomie, Technische 
      Universitat Munchen, Klinikum rechts der Isar, Trogerstr. 18, 81675, Munich, 
      Germany.
FAU - Luber, Birgit
AU  - Luber B
AUID- ORCID: 0000-0002-6900-0944
AD  - Institut fur Allgemeine Pathologie und Pathologische Anatomie, Technische 
      Universitat Munchen, Klinikum rechts der Isar, Trogerstr. 18, 81675, Munich, 
      Germany. birgit.luber@tum.de.
LA  - eng
PT  - Journal Article
DEP - 20161208
PL  - Germany
TA  - J Cancer Res Clin Oncol
JT  - Journal of cancer research and clinical oncology
JID - 7902060
RN  - 0 (Amphiregulin)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Heparin-binding EGF-like Growth Factor)
RN  - 0 (Ligands)
RN  - 0 (Transforming Growth Factor alpha)
RN  - 62229-50-9 (Epidermal Growth Factor)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - P188ANX8CK (Trastuzumab)
RN  - PQX0D8J21J (Cetuximab)
SB  - IM
MH  - Amphiregulin/metabolism
MH  - Antineoplastic Agents/*therapeutic use
MH  - Cell Division/drug effects
MH  - Cell Line, Tumor
MH  - Cetuximab/*therapeutic use
MH  - Epidermal Growth Factor/metabolism
MH  - Heparin-binding EGF-like Growth Factor/metabolism
MH  - Humans
MH  - Ligands
MH  - Prognosis
MH  - Receptor, ErbB-2/*metabolism
MH  - Stomach Neoplasms/*drug therapy/metabolism/pathology
MH  - Transforming Growth Factor alpha/metabolism
MH  - Trastuzumab/*therapeutic use
PMC - PMC5352771
OTO - NOTNLM
OT  - Cetuximab
OT  - EGFR
OT  - Gastric cancer
OT  - HER receptors
OT  - Ligand
OT  - Trastuzumab
COIS- CONFLICT OF INTEREST: We declare that we have no conflict of interest. ETHICAL 
      APPROVAL: This article does not contain any studies with human participants or 
      animals performed by any of the authors.
EDAT- 2016/12/10 06:00
MHDA- 2017/03/21 06:00
PMCR- 2016/12/08
CRDT- 2016/12/10 06:00
PHST- 2016/09/08 00:00 [received]
PHST- 2016/11/17 00:00 [accepted]
PHST- 2016/12/10 06:00 [pubmed]
PHST- 2017/03/21 06:00 [medline]
PHST- 2016/12/10 06:00 [entrez]
PHST- 2016/12/08 00:00 [pmc-release]
AID - 10.1007/s00432-016-2308-z [pii]
AID - 2308 [pii]
AID - 10.1007/s00432-016-2308-z [doi]
PST - ppublish
SO  - J Cancer Res Clin Oncol. 2017 Apr;143(4):573-600. doi: 10.1007/s00432-016-2308-z. 
      Epub 2016 Dec 8.