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Interaction between lung cancer cells and astrocytes via specific inflammatory cytokines in the microenvironment of brain metastasis

The incidence of brain metastasis is increasing, however, little is known about molecular mechanism responsible for lung cancer-derived brain metastasis and their development in the brain. In the present study, brain pathology was examined in an experimental model system of brain metastasis as well...

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Autores principales: Seike, Toshihiro, Fujita, Kyota, Yamakawa, Yukiko, Kido, Mizuho A., Takiguchi, Soichi, Teramoto, Norihiro, Iguchi, Haruo, Noda, Mami
Formato: Texto
Lenguaje:English
Publicado: Springer Netherlands 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2998640/
https://www.ncbi.nlm.nih.gov/pubmed/20953899
http://dx.doi.org/10.1007/s10585-010-9354-8
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author Seike, Toshihiro
Fujita, Kyota
Yamakawa, Yukiko
Kido, Mizuho A.
Takiguchi, Soichi
Teramoto, Norihiro
Iguchi, Haruo
Noda, Mami
author_facet Seike, Toshihiro
Fujita, Kyota
Yamakawa, Yukiko
Kido, Mizuho A.
Takiguchi, Soichi
Teramoto, Norihiro
Iguchi, Haruo
Noda, Mami
author_sort Seike, Toshihiro
collection PubMed
description The incidence of brain metastasis is increasing, however, little is known about molecular mechanism responsible for lung cancer-derived brain metastasis and their development in the brain. In the present study, brain pathology was examined in an experimental model system of brain metastasis as well as in human brain with lung cancer metastasis. In an experimental model, after 3–6 weeks of intracardiac inoculation of human lung cancer-derived (HARA-B) cells in nude mice, wide range of brain metastases were observed. The brain sections showed significant increase in glial fibrillary acidic protein (GFAP)-positive astrocytes around metastatic lesions. To elucidate the role of astrocytes in lung cancer proliferation, the interaction between primary cultured mouse astrocytes and HARA-B cells was analyzed in vitro. Co-cultures and insert-cultures demonstrated that astrocytes were activated by tumor cell-oriented factors; macrophage migration inhibitory factor (MIF), interleukin-8 (IL-8) and plasminogen activator inhibitor-1 (PAI-1). Activated astrocytes produced interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin-1 β (IL-1β), which in turn promoted tumor cell proliferation. Semi-quantitative immunocytochemistry showed that increased expression of receptors for IL-6 and its subunits gp130 on HARA-B cells. Receptors for TNF-α and IL-1β were also detected on HARA-B cells but down-regulated after co-culture with astrocytes. Insert-culture with astrocytes also stimulated the proliferation of other lung cancer-derived cell lines (PC-9, QG56, and EBC-1). These results suggest that tumor cells and astrocytes stimulate each other and these mutual relationships may be important to understand how lung cancer cells metastasize and develop in the brain. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10585-010-9354-8) contains supplementary material, which is available to authorized users.
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spelling pubmed-29986402011-01-04 Interaction between lung cancer cells and astrocytes via specific inflammatory cytokines in the microenvironment of brain metastasis Seike, Toshihiro Fujita, Kyota Yamakawa, Yukiko Kido, Mizuho A. Takiguchi, Soichi Teramoto, Norihiro Iguchi, Haruo Noda, Mami Clin Exp Metastasis Research Paper The incidence of brain metastasis is increasing, however, little is known about molecular mechanism responsible for lung cancer-derived brain metastasis and their development in the brain. In the present study, brain pathology was examined in an experimental model system of brain metastasis as well as in human brain with lung cancer metastasis. In an experimental model, after 3–6 weeks of intracardiac inoculation of human lung cancer-derived (HARA-B) cells in nude mice, wide range of brain metastases were observed. The brain sections showed significant increase in glial fibrillary acidic protein (GFAP)-positive astrocytes around metastatic lesions. To elucidate the role of astrocytes in lung cancer proliferation, the interaction between primary cultured mouse astrocytes and HARA-B cells was analyzed in vitro. Co-cultures and insert-cultures demonstrated that astrocytes were activated by tumor cell-oriented factors; macrophage migration inhibitory factor (MIF), interleukin-8 (IL-8) and plasminogen activator inhibitor-1 (PAI-1). Activated astrocytes produced interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin-1 β (IL-1β), which in turn promoted tumor cell proliferation. Semi-quantitative immunocytochemistry showed that increased expression of receptors for IL-6 and its subunits gp130 on HARA-B cells. Receptors for TNF-α and IL-1β were also detected on HARA-B cells but down-regulated after co-culture with astrocytes. Insert-culture with astrocytes also stimulated the proliferation of other lung cancer-derived cell lines (PC-9, QG56, and EBC-1). These results suggest that tumor cells and astrocytes stimulate each other and these mutual relationships may be important to understand how lung cancer cells metastasize and develop in the brain. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10585-010-9354-8) contains supplementary material, which is available to authorized users. Springer Netherlands 2010-10-17 2011 /pmc/articles/PMC2998640/ /pubmed/20953899 http://dx.doi.org/10.1007/s10585-010-9354-8 Text en © The Author(s) 2010 https://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.
spellingShingle Research Paper
Seike, Toshihiro
Fujita, Kyota
Yamakawa, Yukiko
Kido, Mizuho A.
Takiguchi, Soichi
Teramoto, Norihiro
Iguchi, Haruo
Noda, Mami
Interaction between lung cancer cells and astrocytes via specific inflammatory cytokines in the microenvironment of brain metastasis
title Interaction between lung cancer cells and astrocytes via specific inflammatory cytokines in the microenvironment of brain metastasis
title_full Interaction between lung cancer cells and astrocytes via specific inflammatory cytokines in the microenvironment of brain metastasis
title_fullStr Interaction between lung cancer cells and astrocytes via specific inflammatory cytokines in the microenvironment of brain metastasis
title_full_unstemmed Interaction between lung cancer cells and astrocytes via specific inflammatory cytokines in the microenvironment of brain metastasis
title_short Interaction between lung cancer cells and astrocytes via specific inflammatory cytokines in the microenvironment of brain metastasis
title_sort interaction between lung cancer cells and astrocytes via specific inflammatory cytokines in the microenvironment of brain metastasis
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2998640/
https://www.ncbi.nlm.nih.gov/pubmed/20953899
http://dx.doi.org/10.1007/s10585-010-9354-8
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