The role of adipocytes in the bone tumor micro-environment

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Adipocytes are metabolically active and their number increases with age and obesity, being associated with a variety of metabolic pathologies. For cancer, adipocyte-supplied factors are related to development and progression, in particular for tumors that grow in or metastasize to adipocyte enriched environments like bone. Therefore, our main research question is to elucidate on the role of adipocytes in the bone marrow microenvironment of osteolytic metastasis using small animal models.Our preliminary results indicate that melanoma growth within the bone is enhanced in an adipocyte-rich bone marrow environment, which is consistent with the finding that obesity derived factors induced osteoclastogenesis through cancer cell activation. Adipocytes would therefore adopt an unprecedented role in metastatic bone disease and would represent a novel cellular target to influence the progression of bone metastasis. In this context, investigations on the function of adipocytes in metastatic bone disease during breast cancer and malignant melanoma are needed. Therefore, the aims of the project are the assessment of adipocyte-derived factors as well as the determination of their influence on bone marrow microenvironment and tumor cell growth in the metastatic niche. For this purpose, in vivo and in vitro molecular assays as well as multimodal imaging will be used to investigate processes like tumor cell proliferation, bone resorption and angiogenesis in osteolytic bone metastasis in different models of expansion and loss of bone marrow adipocytes.