Tumor & micro-environment

Numerous mechanisms that are critical for developmental biology are also involved in tumorigenesis. The transcription factors HIFs (Hypoxia Inducible Factors) illustrate this remark, playing fundamental roles both in tumor and skeletal development. The general goal of our work is to study the role of hypoxia and HIFs in skeletal development, and evaluate how their effects within the bone microenvironment could contribute to bone metastasis.
We previously demonstrated that tissue hypoxia and HIF-1alpa are essential to ensure proper skeletal development but the role of HIFs in chondrodysplasias (skeletal disorders characterize by an abnormal development of the growth plate cartilage) is unknown. Our recent work indicates that HIFs are involved in these pathological conditions. We currently investigate how HIFs could contribute to skeletal dysplasia and whether this can be prevented in mice.
HIFs are also essential for bone homeostasis. We recently found that osteoprogenitor cells (OPCs) are hypoxic and express high levels of HIFs. Notably, we demonstrated that activation of HIF signaling n OPCs promotes locally breast cancer metastasis to bone, but also promotes distant tumor growth in the breast and dissemination to the lungs and to other organs located far away from bones. We are currently investigating how the hypoxic bone microenvironment controls breast cancer growth and metastasis in a systemic fashion.