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Clinical & Experimental Metastasis
Published in: Clinical & Experimental Metastasis 7/2011

Open Access 01-10-2011 | Research Paper

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

Authors: Koh Furugaki, Yoichiro Moriya, Toshiki Iwai, Keigo Yorozu, Mieko Yanagisawa, Kumiko Kondoh, Kaori Fujimoto-Ohuchi, Kazushige Mori

Published in: Clinical & Experimental Metastasis | Issue 7/2011

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Abstract

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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Metadata
Title
Erlotinib inhibits osteolytic bone invasion of human non-small-cell lung cancer cell line NCI-H292
Authors
Koh Furugaki
Yoichiro Moriya
Toshiki Iwai
Keigo Yorozu
Mieko Yanagisawa
Kumiko Kondoh
Kaori Fujimoto-Ohuchi
Kazushige Mori
Publication date
01-10-2011
Publisher
Springer Netherlands
Published in
Clinical & Experimental Metastasis / Issue 7/2011
Print ISSN: 0262-0898
Electronic ISSN: 1573-7276
DOI
https://doi.org/10.1007/s10585-011-9398-4

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