Erlotinib inhibits osteolytic bone invasion of human non-small-cell lung cancer cell line NCI-H292Reportar como inadecuado

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Clinical and Experimental Metastasis

, Volume 28, Issue 7, pp 649–659

First Online: 18 June 2011Received: 05 January 2011Accepted: 31 May 2011DOI: 10.1007-s10585-011-9398-4

Cite this article as: Furugaki, K., Moriya, Y., Iwai, T. et al. Clin Exp Metastasis 2011 28: 649. doi:10.1007-s10585-011-9398-4


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.

KeywordsEpidermal growth factor receptor Tyrosine kinase inhibitor Osteolytic bone invasion model Osteoclast AbbreviationEGFREpidermal growth factor receptor

NSCLCNon-small-cell lung cancer

PTHrPParathyroid hormone-related protein

VEGFVascular endothelial growth factor

SRESkeletal-related event

TKITyrosine kinase inhibitor

MEMMinimum essential medium

HEHematoxylin and eosin

TRAPTartrate-resistant acid phosphatase

ALPAlkaline phosphatase


RANKLReceptor activator of NF-κB ligand

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Autor: Koh Furugaki - Yoichiro Moriya - Toshiki Iwai - Keigo Yorozu - Mieko Yanagisawa - Kumiko Kondoh - Kaori Fujimoto-Ohuchi - K


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