The systemic control of breast cancer by the skeleton
The importance of the bone microenvironment in cancer biology has been well illustrated in the case of breast cancer metastasis to bone, but its impact on cancer progression outside the skeleton had never been evaluated until recently. Interestingly, previous clinical data showed that women with high bone mass have a higher risk of developing breast tumors. This observation was important since it suggested that the bone microenvironment, which controls bone mass, could remotely influence breast cancer by an unknown mechanism. Using genetic models and pharmacological approaches in mice, we discovered the mechanism by which activation of the hypoxia inducible factor 1 in osteoblast lineages cells promotes breast cancer growth and metastasis, in a systemic fashion. We also found evidence that osteoblasts can mediate distant tumorigenic effects upon activation of additional signals, and that drugs used in clinic that affect bone homeostasis can have important consequences in cancer progression. These aspects will be presented in the context of breast cancer, but the influence of the osteoblasts in other types of cancers will be briefly discussed as well.
INSERM U1132, Hôpital Lariboisière, Paris, France
Domain 1 - UMR 3347 / U1021 - Normal and pathological signaling