---
_id: '8093'
abstract:
- lang: eng
text: "Background: The activation of the EGFR/Ras-signalling pathway in tumour cells
induces a distinct chemokine repertoire, which in turn modulates the tumour microenvironment.\r\nMethods:
The effects of EGFR/Ras on the expression and translation of CCL20 were analysed
in a large set of epithelial cancer cell lines and tumour tissues by RT-qPCR and
ELISA in vitro. CCL20 production was verified by immunohistochemistry in different
tumour tissues and correlated with clinical data. The effects of CCL20 on endothelial
cell migration and tumour-associated vascularisation were comprehensively analysed
with chemotaxis assays in vitro and in CCR6-deficient mice in vivo.\r\nResults:
Tumours facilitate progression by the EGFR/Ras-induced production of CCL20. Expression
of the chemokine CCL20 in tumours correlates with advanced tumour stage, increased
lymph node metastasis and decreased survival in patients. Microvascular endothelial
cells abundantly express the specific CCL20 receptor CCR6. CCR6 signalling in
endothelial cells induces angiogenesis. CCR6-deficient mice show significantly
decreased tumour growth and tumour-associated vascularisation. The observed phenotype
is dependent on CCR6 deficiency in stromal cells but not within the immune system.\r\nConclusion:
We propose that the chemokine axis CCL20–CCR6 represents a novel and promising
target to interfere with the tumour microenvironment, and opens an innovative
multimodal strategy for cancer therapy."
acknowledgement: "The authors would like to thank A. van Lierop for technical assistance.
In addition, we thank C. Dullin, J. Missbach-Güntner and S. Greco for advice and
assistance with fpVCT imaging. Furthermore, the authors would like to thank H. K.
Horst for advice on performing matrigel plug assays. This study has also been partially
presented in A. Schorr’s doctoral thesis and the funding report of the SPP 1190
‘The tumor-vessel interface’ of the ‘Deutsche Forschungsgemeinschaft’ (DFG).\r\nThis
project was funded by the SPP 1190 “The tumor-vessel interface” and HO 2092/8-1
of the ‘Deutsche Forschungsgemeinschaft’ (DFG) to B. Homey. In addition, it was
supported by grants from the Austrian Science Fund (FWF, W1212 to N. Amberg and
J. Klufa and I4300-B to T. Bauer), the WWTF project LS16-025 and the European Research
Council (ERC) Advanced grant (ERC-2015-AdG TNT-Tumors 694883) to M. Sibilia."
article_processing_charge: No
article_type: original
author:
- first_name: Andreas
full_name: Hippe, Andreas
last_name: Hippe
- first_name: Stephan Alexander
full_name: Braun, Stephan Alexander
last_name: Braun
- first_name: Péter
full_name: Oláh, Péter
last_name: Oláh
- first_name: Peter Arne
full_name: Gerber, Peter Arne
last_name: Gerber
- first_name: Anne
full_name: Schorr, Anne
last_name: Schorr
- first_name: Stephan
full_name: Seeliger, Stephan
last_name: Seeliger
- first_name: Stephanie
full_name: Holtz, Stephanie
last_name: Holtz
- first_name: Katharina
full_name: Jannasch, Katharina
last_name: Jannasch
- first_name: Andor
full_name: Pivarcsi, Andor
last_name: Pivarcsi
- first_name: Bettina
full_name: Buhren, Bettina
last_name: Buhren
- first_name: Holger
full_name: Schrumpf, Holger
last_name: Schrumpf
- first_name: Andreas
full_name: Kislat, Andreas
last_name: Kislat
- first_name: Erich
full_name: Bünemann, Erich
last_name: Bünemann
- first_name: Martin
full_name: Steinhoff, Martin
last_name: Steinhoff
- first_name: Jens
full_name: Fischer, Jens
last_name: Fischer
- first_name: Sérgio A.
full_name: Lira, Sérgio A.
last_name: Lira
- first_name: Petra
full_name: Boukamp, Petra
last_name: Boukamp
- first_name: Peter
full_name: Hevezi, Peter
last_name: Hevezi
- first_name: Nikolas Hendrik
full_name: Stoecklein, Nikolas Hendrik
last_name: Stoecklein
- first_name: Thomas
full_name: Hoffmann, Thomas
last_name: Hoffmann
- first_name: Frauke
full_name: Alves, Frauke
last_name: Alves
- first_name: Jonathan
full_name: Sleeman, Jonathan
last_name: Sleeman
- first_name: Thomas
full_name: Bauer, Thomas
last_name: Bauer
- first_name: Jörg
full_name: Klufa, Jörg
last_name: Klufa
- first_name: Nicole
full_name: Amberg, Nicole
id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87
last_name: Amberg
orcid: 0000-0002-3183-8207
- first_name: Maria
full_name: Sibilia, Maria
last_name: Sibilia
- first_name: Albert
full_name: Zlotnik, Albert
last_name: Zlotnik
- first_name: Anja
full_name: Müller-Homey, Anja
last_name: Müller-Homey
- first_name: Bernhard
full_name: Homey, Bernhard
last_name: Homey
citation:
ama: Hippe A, Braun SA, Oláh P, et al. EGFR/Ras-induced CCL20 production modulates
the tumour microenvironment. British Journal of Cancer. 2020;123:942-954.
doi:10.1038/s41416-020-0943-2
apa: Hippe, A., Braun, S. A., Oláh, P., Gerber, P. A., Schorr, A., Seeliger, S.,
… Homey, B. (2020). EGFR/Ras-induced CCL20 production modulates the tumour microenvironment.
British Journal of Cancer. Springer Nature. https://doi.org/10.1038/s41416-020-0943-2
chicago: Hippe, Andreas, Stephan Alexander Braun, Péter Oláh, Peter Arne Gerber,
Anne Schorr, Stephan Seeliger, Stephanie Holtz, et al. “EGFR/Ras-Induced CCL20
Production Modulates the Tumour Microenvironment.” British Journal of Cancer.
Springer Nature, 2020. https://doi.org/10.1038/s41416-020-0943-2.
ieee: A. Hippe et al., “EGFR/Ras-induced CCL20 production modulates the tumour
microenvironment,” British Journal of Cancer, vol. 123. Springer Nature,
pp. 942–954, 2020.
ista: Hippe A, Braun SA, Oláh P, Gerber PA, Schorr A, Seeliger S, Holtz S, Jannasch
K, Pivarcsi A, Buhren B, Schrumpf H, Kislat A, Bünemann E, Steinhoff M, Fischer
J, Lira SA, Boukamp P, Hevezi P, Stoecklein NH, Hoffmann T, Alves F, Sleeman J,
Bauer T, Klufa J, Amberg N, Sibilia M, Zlotnik A, Müller-Homey A, Homey B. 2020.
EGFR/Ras-induced CCL20 production modulates the tumour microenvironment. British
Journal of Cancer. 123, 942–954.
mla: Hippe, Andreas, et al. “EGFR/Ras-Induced CCL20 Production Modulates the Tumour
Microenvironment.” British Journal of Cancer, vol. 123, Springer Nature,
2020, pp. 942–54, doi:10.1038/s41416-020-0943-2.
short: A. Hippe, S.A. Braun, P. Oláh, P.A. Gerber, A. Schorr, S. Seeliger, S. Holtz,
K. Jannasch, A. Pivarcsi, B. Buhren, H. Schrumpf, A. Kislat, E. Bünemann, M. Steinhoff,
J. Fischer, S.A. Lira, P. Boukamp, P. Hevezi, N.H. Stoecklein, T. Hoffmann, F.
Alves, J. Sleeman, T. Bauer, J. Klufa, N. Amberg, M. Sibilia, A. Zlotnik, A. Müller-Homey,
B. Homey, British Journal of Cancer 123 (2020) 942–954.
date_created: 2020-07-05T22:00:46Z
date_published: 2020-09-15T00:00:00Z
date_updated: 2023-08-22T07:51:12Z
day: '15'
ddc:
- '610'
department:
- _id: SiHi
doi: 10.1038/s41416-020-0943-2
external_id:
isi:
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pmid:
- '32601464'
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month: '09'
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page: 942-954
pmid: 1
publication: British Journal of Cancer
publication_identifier:
eissn:
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issn:
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publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
link:
- relation: erratum
url: https://doi.org/10.1038/s41416-021-01563-y
record:
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relation: later_version
status: deleted
scopus_import: '1'
status: public
title: EGFR/Ras-induced CCL20 production modulates the tumour microenvironment
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
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...