BoneKEy Reports | BoneKEy Watch
Role of insulin-like growth factor 1 in bone metastasis
DOI:10.1038/bonekey.2012.170
A mouse model of bone metastasis from breast cancer using calvarial bone, usually a rare site for bone metastases after intracardiac inoculation of cancer cells, was used to demonstrate that local stimulation with IL-1β created osteolytic lesions. These lesions provided colonization sites for metastatic cancer cells. Inhibiting bone resorption inhibited bone metastasis.
Hiraga et al. then identified raised levels of insulin-like growth factor 1 (IGF-1) in the supernatant obtained from culturing resorbed bones and showed that blocking IGF-1 inhibited the development of bone metastases. In samples obtained from human cancer patients with bone metastases, over 86% showed elevated expression of the receptor for IGF-1 (IGF1R). Further experiments suggested that IGF-1 produced by resorbed bone activates the IGF1R/Akt/ NF-κB signaling pathway, allowing communication between bone and circulating cancer cells.
Editor's comment: Once metastatic breast cells are in the bone marrow, they promote osteoclast-mediated bone resorption and hijack signals coming from the resorbed bone matrix. In this respect, bone-derived growth factors including transforming growth factor-beta, fibroblast growth factor, platelet-derived growth factor and calcium support cancer cell growth. Here, Hiraga and colleagues provide strong evidence that IGF is another bone-derived growth factor playing a key role in the development of bone metastases from breast cancer. The signaling pathway identified may provide opportunities for therapeutic intervention.
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