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Imatinib mesylate suppresses bone metastases of breast cancer by inhibiting osteoclasts through the blockade of c-Fms signals by Toru Hiraga; Hiroaki Nakamura is a Medicine article available to read on EtoBox.

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## Abstract Imatinib mesylate (imatinib) is a potent and selective inhibitor of the tyrosine kinases, Bcr‐Abl, c‐Kit and platelet‐derived growth factor receptors (PDGFRs). Recently, it has been reported that imatinib also targets the macrophage colony‐stimulating factor (M‐CSF) receptor c‐Fms. M‐CSF signals are essential for the differentiation of osteoclasts. Bone metastases of breast cancer are frequently associated with osteoclastic bone destruction. Furthermore, several lines of evidence suggest that osteoclasts play central roles in the development and progression of bone metastases. Thus, in the present study, we examined the effects of imatinib on bone metastases of breast cancer. Coimmunoprecipitation assays showed that imatinib inhibited the M‐CSF‐induced phosphorylation of c‐Fms in osteoclast precursor cells as well as the PDGF‐induced PDGFR phosphorylation in MDA‐MB‐231 human breast cancer cells. Imatinib also markedly reduced osteoclast formation __in vitro__. In contrast, those concentrations of imatinib did not affect osteoblast differentiation. We then examined the effects of imatinib on bone metastases of MDA‐MB‐231 cells in a nude mouse model. Radiographic and hist

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Author

Toru Hiraga; Hiroaki Nakamura

Publisher

John Wiley and Sons; Wiley (John Wiley & Sons); John Wiley & Sons Inc.; Wiley; Research Square; Test accounts (ISSN 0020-7136)

Published

2008

Language

EN

Field

Medicine (Health Sciences)