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Hepatocyte Nuclear Factor (HNF)‐4α Induces Expression of Endothelial Fas Ligand (FasL) to Prevent Cancer Cell Transmigration: A Novel Defense Mechanism of Endothelium against Cancer Metastasis

Endothelial Fas ligand (FasL) contributes to the “immune privilege” of tissues such as testis and eye, in which apoptosis is induced in infiltrating Fas‐positive activated T cells and results in the inhibition of leukocyte extravasation. In this study, we examined the role of endothelial FasL in con...

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Autores principales: Osanai, Makoto, Chiba, Hideki, Kojima, Takashi, Fujibe, Masato, Kuwahara, Kazuhide, Kimura, Hiromichi, Satoh, Masaaki, Sawada, Norimasa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 2002
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5927027/
https://www.ncbi.nlm.nih.gov/pubmed/12036449
http://dx.doi.org/10.1111/j.1349-7006.2002.tb01288.x
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author Osanai, Makoto
Chiba, Hideki
Kojima, Takashi
Fujibe, Masato
Kuwahara, Kazuhide
Kimura, Hiromichi
Satoh, Masaaki
Sawada, Norimasa
author_facet Osanai, Makoto
Chiba, Hideki
Kojima, Takashi
Fujibe, Masato
Kuwahara, Kazuhide
Kimura, Hiromichi
Satoh, Masaaki
Sawada, Norimasa
author_sort Osanai, Makoto
collection PubMed
description Endothelial Fas ligand (FasL) contributes to the “immune privilege” of tissues such as testis and eye, in which apoptosis is induced in infiltrating Fas‐positive activated T cells and results in the inhibition of leukocyte extravasation. In this study, we examined the role of endothelial FasL in controlling cancer cell transmigration using rat lung endothelial (RLE) cell line bearing a doxycycline‐inducible hepatocyte nuclear factor (HNF)‐4α expression system. We showed that a detectable level of FasL was expressed in RLE cells and that this expression was markedly up‐regulated and well correlated to the degree of HNF–4α expression in a time‐dependent manner. When various cancer cells were overlaid on an RLE monolayer sheet, we examined the ability of endothelial FasL to induce massive apoptosis in Fas‐expressing cancer cells and found a causal link to inhibition of the transmigration. Finally, we showed that FasL was expressed in capillaries of the rat brain by immunohistochemical staining, suggesting that FasL serves its functions not only in vitro, but also in vivo. These results raise the possibility that HNF–4α is involved in regulating cancer cell transmigration by modulating the Fas‐FasL system.
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spelling pubmed-59270272018-05-11 Hepatocyte Nuclear Factor (HNF)‐4α Induces Expression of Endothelial Fas Ligand (FasL) to Prevent Cancer Cell Transmigration: A Novel Defense Mechanism of Endothelium against Cancer Metastasis Osanai, Makoto Chiba, Hideki Kojima, Takashi Fujibe, Masato Kuwahara, Kazuhide Kimura, Hiromichi Satoh, Masaaki Sawada, Norimasa Jpn J Cancer Res Article Endothelial Fas ligand (FasL) contributes to the “immune privilege” of tissues such as testis and eye, in which apoptosis is induced in infiltrating Fas‐positive activated T cells and results in the inhibition of leukocyte extravasation. In this study, we examined the role of endothelial FasL in controlling cancer cell transmigration using rat lung endothelial (RLE) cell line bearing a doxycycline‐inducible hepatocyte nuclear factor (HNF)‐4α expression system. We showed that a detectable level of FasL was expressed in RLE cells and that this expression was markedly up‐regulated and well correlated to the degree of HNF–4α expression in a time‐dependent manner. When various cancer cells were overlaid on an RLE monolayer sheet, we examined the ability of endothelial FasL to induce massive apoptosis in Fas‐expressing cancer cells and found a causal link to inhibition of the transmigration. Finally, we showed that FasL was expressed in capillaries of the rat brain by immunohistochemical staining, suggesting that FasL serves its functions not only in vitro, but also in vivo. These results raise the possibility that HNF–4α is involved in regulating cancer cell transmigration by modulating the Fas‐FasL system. Blackwell Publishing Ltd 2002-05 /pmc/articles/PMC5927027/ /pubmed/12036449 http://dx.doi.org/10.1111/j.1349-7006.2002.tb01288.x Text en
spellingShingle Article
Osanai, Makoto
Chiba, Hideki
Kojima, Takashi
Fujibe, Masato
Kuwahara, Kazuhide
Kimura, Hiromichi
Satoh, Masaaki
Sawada, Norimasa
Hepatocyte Nuclear Factor (HNF)‐4α Induces Expression of Endothelial Fas Ligand (FasL) to Prevent Cancer Cell Transmigration: A Novel Defense Mechanism of Endothelium against Cancer Metastasis
title Hepatocyte Nuclear Factor (HNF)‐4α Induces Expression of Endothelial Fas Ligand (FasL) to Prevent Cancer Cell Transmigration: A Novel Defense Mechanism of Endothelium against Cancer Metastasis
title_full Hepatocyte Nuclear Factor (HNF)‐4α Induces Expression of Endothelial Fas Ligand (FasL) to Prevent Cancer Cell Transmigration: A Novel Defense Mechanism of Endothelium against Cancer Metastasis
title_fullStr Hepatocyte Nuclear Factor (HNF)‐4α Induces Expression of Endothelial Fas Ligand (FasL) to Prevent Cancer Cell Transmigration: A Novel Defense Mechanism of Endothelium against Cancer Metastasis
title_full_unstemmed Hepatocyte Nuclear Factor (HNF)‐4α Induces Expression of Endothelial Fas Ligand (FasL) to Prevent Cancer Cell Transmigration: A Novel Defense Mechanism of Endothelium against Cancer Metastasis
title_short Hepatocyte Nuclear Factor (HNF)‐4α Induces Expression of Endothelial Fas Ligand (FasL) to Prevent Cancer Cell Transmigration: A Novel Defense Mechanism of Endothelium against Cancer Metastasis
title_sort hepatocyte nuclear factor (hnf)‐4α induces expression of endothelial fas ligand (fasl) to prevent cancer cell transmigration: a novel defense mechanism of endothelium against cancer metastasis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5927027/
https://www.ncbi.nlm.nih.gov/pubmed/12036449
http://dx.doi.org/10.1111/j.1349-7006.2002.tb01288.x
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