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Erlotinib inhibits osteolytic bone invasion of human non-small-cell lung cancer cell line NCI-H292

Previous preclinical and clinical findings have suggested a potential role of epidermal growth factor receptor (EGFR) in osteoclast differentiation and the pathogenesis of bone metastasis in cancer. In this study, we investigated the effect of erlotinib, an orally active EGFR tyrosine kinase inhibit...

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Autores principales: Furugaki, Koh, Moriya, Yoichiro, Iwai, Toshiki, Yorozu, Keigo, Yanagisawa, Mieko, Kondoh, Kumiko, Fujimoto-Ohuchi, Kaori, Mori, Kazushige
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Netherlands 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3198194/
https://www.ncbi.nlm.nih.gov/pubmed/21688034
http://dx.doi.org/10.1007/s10585-011-9398-4
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author Furugaki, Koh
Moriya, Yoichiro
Iwai, Toshiki
Yorozu, Keigo
Yanagisawa, Mieko
Kondoh, Kumiko
Fujimoto-Ohuchi, Kaori
Mori, Kazushige
author_facet Furugaki, Koh
Moriya, Yoichiro
Iwai, Toshiki
Yorozu, Keigo
Yanagisawa, Mieko
Kondoh, Kumiko
Fujimoto-Ohuchi, Kaori
Mori, Kazushige
author_sort Furugaki, Koh
collection PubMed
description Previous preclinical and clinical findings have suggested a potential role of epidermal growth factor receptor (EGFR) in osteoclast differentiation and the pathogenesis of bone metastasis in cancer. In this study, we investigated the effect of erlotinib, an orally active EGFR tyrosine kinase inhibitor (TKI), on the bone invasion of human non-small-cell lung cancer (NSCLC) cell line NCI-H292. First, we established a novel osteolytic bone invasion model of NCI-H292 cells which was made by inoculating cancer cells into the tibia of scid mice. In this model, NCI-H292 cells markedly activated osteoclasts in tibia, which resulted in osteolytic bone destruction. Erlotinib treatment suppressed osteoclast activation to the basal level through suppressing receptor activator of NF-κB ligand (RANKL) expression in osteoblast/stromal cell at the bone metastatic sites, which leads to inhibition of osteolytic bone destruction caused by NCI-H292 cells. Erlotinib inhibited the proliferation of NCI-H292 cells in in vitro. Erlotinib suppressed the production of osteolytic factors, such as parathyroid hormone-related protein (PTHrP), IL-8, IL-11 and vascular endothelial growth factor (VEGF) in NCI-H292 cells. Furthermore, erlotinib also inhibited osteoblast/stromal cell proliferation in vitro and the development of osteoclasts induced by RANKL in vitro. In conclusion, erlotinib inhibits tumor-induced osteolytic invasion in bone metastasis by suppressing osteoclast activation through inhibiting tumor growth at the bone metastatic sites, osteolytic factor production in tumor cells, osteoblast/stromal cell proliferation and osteoclast differentiation from mouse bone marrow cells.
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spelling pubmed-31981942011-11-10 Erlotinib inhibits osteolytic bone invasion of human non-small-cell lung cancer cell line NCI-H292 Furugaki, Koh Moriya, Yoichiro Iwai, Toshiki Yorozu, Keigo Yanagisawa, Mieko Kondoh, Kumiko Fujimoto-Ohuchi, Kaori Mori, Kazushige Clin Exp Metastasis Research Paper Previous preclinical and clinical findings have suggested a potential role of epidermal growth factor receptor (EGFR) in osteoclast differentiation and the pathogenesis of bone metastasis in cancer. In this study, we investigated the effect of erlotinib, an orally active EGFR tyrosine kinase inhibitor (TKI), on the bone invasion of human non-small-cell lung cancer (NSCLC) cell line NCI-H292. First, we established a novel osteolytic bone invasion model of NCI-H292 cells which was made by inoculating cancer cells into the tibia of scid mice. In this model, NCI-H292 cells markedly activated osteoclasts in tibia, which resulted in osteolytic bone destruction. Erlotinib treatment suppressed osteoclast activation to the basal level through suppressing receptor activator of NF-κB ligand (RANKL) expression in osteoblast/stromal cell at the bone metastatic sites, which leads to inhibition of osteolytic bone destruction caused by NCI-H292 cells. Erlotinib inhibited the proliferation of NCI-H292 cells in in vitro. Erlotinib suppressed the production of osteolytic factors, such as parathyroid hormone-related protein (PTHrP), IL-8, IL-11 and vascular endothelial growth factor (VEGF) in NCI-H292 cells. Furthermore, erlotinib also inhibited osteoblast/stromal cell proliferation in vitro and the development of osteoclasts induced by RANKL in vitro. In conclusion, erlotinib inhibits tumor-induced osteolytic invasion in bone metastasis by suppressing osteoclast activation through inhibiting tumor growth at the bone metastatic sites, osteolytic factor production in tumor cells, osteoblast/stromal cell proliferation and osteoclast differentiation from mouse bone marrow cells. Springer Netherlands 2011-06-18 2011 /pmc/articles/PMC3198194/ /pubmed/21688034 http://dx.doi.org/10.1007/s10585-011-9398-4 Text en © The Author(s) 2011 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
Furugaki, Koh
Moriya, Yoichiro
Iwai, Toshiki
Yorozu, Keigo
Yanagisawa, Mieko
Kondoh, Kumiko
Fujimoto-Ohuchi, Kaori
Mori, Kazushige
Erlotinib inhibits osteolytic bone invasion of human non-small-cell lung cancer cell line NCI-H292
title Erlotinib inhibits osteolytic bone invasion of human non-small-cell lung cancer cell line NCI-H292
title_full Erlotinib inhibits osteolytic bone invasion of human non-small-cell lung cancer cell line NCI-H292
title_fullStr Erlotinib inhibits osteolytic bone invasion of human non-small-cell lung cancer cell line NCI-H292
title_full_unstemmed Erlotinib inhibits osteolytic bone invasion of human non-small-cell lung cancer cell line NCI-H292
title_short Erlotinib inhibits osteolytic bone invasion of human non-small-cell lung cancer cell line NCI-H292
title_sort erlotinib inhibits osteolytic bone invasion of human non-small-cell lung cancer cell line nci-h292
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3198194/
https://www.ncbi.nlm.nih.gov/pubmed/21688034
http://dx.doi.org/10.1007/s10585-011-9398-4
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