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Carcinoma cells misuse the host tissue damage response to invade the brain

The metastatic colonization of the brain by carcinoma cells is still barely understood, in particular when considering interactions with the host tissue. The colonization comes with a substantial destruction of the surrounding host tissue. This leads to activation of damage responses by resident inn...

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Autores principales: Chuang, Han-Ning, van Rossum, Denise, Sieger, Dirk, Siam, Laila, Klemm, Florian, Bleckmann, Annalen, Bayerlová, Michaela, Farhat, Katja, Scheffel, Jörg, Schulz, Matthias, Dehghani, Faramarz, Stadelmann, Christine, Hanisch, Uwe-Karsten, Binder, Claudia, Pukrop, Tobias
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3842117/
https://www.ncbi.nlm.nih.gov/pubmed/23832647
http://dx.doi.org/10.1002/glia.22518
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author Chuang, Han-Ning
van Rossum, Denise
Sieger, Dirk
Siam, Laila
Klemm, Florian
Bleckmann, Annalen
Bayerlová, Michaela
Farhat, Katja
Scheffel, Jörg
Schulz, Matthias
Dehghani, Faramarz
Stadelmann, Christine
Hanisch, Uwe-Karsten
Binder, Claudia
Pukrop, Tobias
author_facet Chuang, Han-Ning
van Rossum, Denise
Sieger, Dirk
Siam, Laila
Klemm, Florian
Bleckmann, Annalen
Bayerlová, Michaela
Farhat, Katja
Scheffel, Jörg
Schulz, Matthias
Dehghani, Faramarz
Stadelmann, Christine
Hanisch, Uwe-Karsten
Binder, Claudia
Pukrop, Tobias
author_sort Chuang, Han-Ning
collection PubMed
description The metastatic colonization of the brain by carcinoma cells is still barely understood, in particular when considering interactions with the host tissue. The colonization comes with a substantial destruction of the surrounding host tissue. This leads to activation of damage responses by resident innate immune cells to protect, repair, and organize the wound healing, but may distract from tumoricidal actions. We recently demonstrated that microglia, innate immune cells of the CNS, assist carcinoma cell invasion. Here we report that this is a fatal side effect of a physiological damage response of the brain tissue. In a brain slice coculture model, contact with both benign and malignant epithelial cells induced a response by microglia and astrocytes comparable to that seen at the interface of human cerebral metastases. While the glial damage response intended to protect the brain from intrusion of benign epithelial cells by inducing apoptosis, it proved ineffective against various malignant cell types. They did not undergo apoptosis and actually exploited the local tissue reaction to invade instead. Gene expression and functional analyses revealed that the C-X-C chemokine receptor type 4 (CXCR4) and WNT signaling were involved in this process. Furthermore, CXCR4-regulated microglia were recruited to sites of brain injury in a zebrafish model and CXCR4 was expressed in human stroke patients, suggesting a conserved role in damage responses to various types of brain injuries. Together, our findings point to a detrimental misuse of the glial damage response program by carcinoma cells resistant to glia-induced apoptosis.
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spelling pubmed-38421172013-12-02 Carcinoma cells misuse the host tissue damage response to invade the brain Chuang, Han-Ning van Rossum, Denise Sieger, Dirk Siam, Laila Klemm, Florian Bleckmann, Annalen Bayerlová, Michaela Farhat, Katja Scheffel, Jörg Schulz, Matthias Dehghani, Faramarz Stadelmann, Christine Hanisch, Uwe-Karsten Binder, Claudia Pukrop, Tobias Glia Original Research Articles The metastatic colonization of the brain by carcinoma cells is still barely understood, in particular when considering interactions with the host tissue. The colonization comes with a substantial destruction of the surrounding host tissue. This leads to activation of damage responses by resident innate immune cells to protect, repair, and organize the wound healing, but may distract from tumoricidal actions. We recently demonstrated that microglia, innate immune cells of the CNS, assist carcinoma cell invasion. Here we report that this is a fatal side effect of a physiological damage response of the brain tissue. In a brain slice coculture model, contact with both benign and malignant epithelial cells induced a response by microglia and astrocytes comparable to that seen at the interface of human cerebral metastases. While the glial damage response intended to protect the brain from intrusion of benign epithelial cells by inducing apoptosis, it proved ineffective against various malignant cell types. They did not undergo apoptosis and actually exploited the local tissue reaction to invade instead. Gene expression and functional analyses revealed that the C-X-C chemokine receptor type 4 (CXCR4) and WNT signaling were involved in this process. Furthermore, CXCR4-regulated microglia were recruited to sites of brain injury in a zebrafish model and CXCR4 was expressed in human stroke patients, suggesting a conserved role in damage responses to various types of brain injuries. Together, our findings point to a detrimental misuse of the glial damage response program by carcinoma cells resistant to glia-induced apoptosis. Blackwell Publishing Ltd 2013-08 2013-07-06 /pmc/articles/PMC3842117/ /pubmed/23832647 http://dx.doi.org/10.1002/glia.22518 Text en Copyright © 2013 Wiley Periodicals, Inc. http://creativecommons.org/licenses/by/2.5/ Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation.
spellingShingle Original Research Articles
Chuang, Han-Ning
van Rossum, Denise
Sieger, Dirk
Siam, Laila
Klemm, Florian
Bleckmann, Annalen
Bayerlová, Michaela
Farhat, Katja
Scheffel, Jörg
Schulz, Matthias
Dehghani, Faramarz
Stadelmann, Christine
Hanisch, Uwe-Karsten
Binder, Claudia
Pukrop, Tobias
Carcinoma cells misuse the host tissue damage response to invade the brain
title Carcinoma cells misuse the host tissue damage response to invade the brain
title_full Carcinoma cells misuse the host tissue damage response to invade the brain
title_fullStr Carcinoma cells misuse the host tissue damage response to invade the brain
title_full_unstemmed Carcinoma cells misuse the host tissue damage response to invade the brain
title_short Carcinoma cells misuse the host tissue damage response to invade the brain
title_sort carcinoma cells misuse the host tissue damage response to invade the brain
topic Original Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3842117/
https://www.ncbi.nlm.nih.gov/pubmed/23832647
http://dx.doi.org/10.1002/glia.22518
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