Imatinib suppresses breast cancer bone metastases by inhibiting osteoclasts

NEW YORK (Reuters Health) - Imatinib mesylate suppresses bone metastases from breast cancer by blocking signals from the macrophage colony-stimulating factor (M-CSF) receptor c-Fms and thereby inhibiting osteoclasts, according to a report in the January 1st International Journal of Cancer.

"In addition to the direct anti-cancer effects, imatinib also has an inhibitory effect on osteoclasts, the key player in the development of bone metastases," Dr. Toru Hiraga told Reuters Health.

Dr. Hiraga and Dr. Hiraoki Nakamura from Matsumoto Dental University, Shiojiri, Nagano, Japan, investigated the effects of imatinib on bone metastases of breast cancer with a special focus on osteoclasts.

Imatinib attenuated the phosphorylation of c-Fms induced by M-CSF in mouse osteoclasts, the authors report, and dose dependently inhibited osteoclast-like cell formation induced by M-CSF and receptor activator of nuclear factor kappa-beta ligand (RANKL).

Imatinib also induced apoptosis in osteoclast precursors, but not at the low doses used to inhibit osteoclast differentiation.

Moreover, the researchers note, the lower concentrations of imatinib used to suppress osteoclast differentiation did not affect osteoblast differentiation.

In nude mice bearing bone metastases, imatinib significantly decreased the number and area of osteolytic lesions, as well as the metastatic tumor burden and osteoclast number in bone metastases, the investigators say, and these effects were reproduced by specific inhibition of c-Fms.

"The inhibitory effects of imatinib against osteoclastic bone resorption may provide a beneficial effect on cancer-induced bone loss, one of the frequent complications caused by hormonal therapy and chemotherapy," Dr. Hiraga concluded.

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