Editors' ChoiceProstate Cancer

Bone Metastases in Prostate Cancer: Finding the Achilles' Heel

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Science Translational Medicine  13 Jan 2010:
Vol. 2, Issue 14, pp. 14ec5
DOI: 10.1126/scitranslmed.3000806

Bone metastases are often seen in patients with advanced prostate cancer. Although various nonspecific treatments such as radiation or hormone therapy are used to manage patients with metastases, our ignorance of the mechanism by which prostate cancer cells preferentially metastasize to bone has precluded any specific therapies for this painful aspect of advanced prostate cancer. In a recent article by Kimura et al., the authors examined whether insulin-like growth factor (IGF)-II might mediate proliferation of prostate cancer cells in human bone, which is a robust source of IGF-II. The authors have developed a clever experimental system in which they place small fragments of adult human bone into mouse fat pads and then inject human prostate cancer cells directly into the implanted bone marrow, where they grow into tumors. Using a newly developed human monoclonal antibody specific for IGF-II, the authors then treated mice carrying human prostate cancer cells with or without associated human bone in order to determine whether the cells depended on IGF-II for growth. They observed a striking reduction in the volumes of the bone-residing prostate tumors, as well as proliferation and prostate-specific antigen (PSA) production, in animals treated with even low concentrations of monoclonal antibody. Furthermore, the effects of IGF-II blockade required the presence of human bone and were mediated by the AKT signaling pathway.

Studies on human prostate cancer metastases are difficult because available tissue is limited, so the ability to model a human bone environment capable of prostate cancer cell engraftment in mice is an exciting development. The identification of IGF-II as a potent trophic cytokine for prostate cancer cells in bone suggests that it may contribute to the organ specificity of prostate cancer metastasis and could also provide an accessible target for therapy.

T. Kimura et al., Targeting of bone-derived insulin-like growth factor-II by a human neutralizing antibody suppresses the growth of prostate cancer cells in a human bone environment. Clin. Can. Res. 16, 121–129 (2010). [Abstract]

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