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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...
Autores principales: | , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Springer Netherlands
2010
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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. |
format | Text |
id | pubmed-2998640 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Springer Netherlands |
record_format | MEDLINE/PubMed |
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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