The role of adipocytes in the bone tumor micro-environment

脂肪细胞具有代谢活性，其数量随着年龄和肥胖的增加而增加，这与各种代谢病理有关。对于癌症，脂肪细胞提供的因子与发育和进展有关，特别是对于生长在脂肪细胞丰富的环境中或转移到脂肪细胞丰富的环境(如骨骼)的肿瘤。因此，我们的主要研究问题是通过小动物模型阐明脂肪细胞在溶骨转移的骨髓微环境中的作用。我们的初步结果表明，在富含脂肪细胞的骨髓环境中，骨内黑色素瘤的生长被促进，这与肥胖衍生因子通过癌细胞激活诱导破骨细胞生成的发现一致。因此，脂肪细胞将在转移性骨疾病中发挥前所未有的作用，并将成为影响骨转移进展的新的细胞靶点。在此背景下，需要研究脂肪细胞在乳腺癌和恶性黑色素瘤转移性骨疾病中的功能。因此，该项目的目标是评估脂肪细胞衍生因子，以及确定它们对转移壁龛中的骨髓微环境和肿瘤细胞生长的影响。为此，将利用体内和体外分子分析以及多模式成像来研究不同骨髓脂肪细胞扩张和丢失模型下溶骨性骨转移中肿瘤细胞的增殖、骨吸收和血管生成等过程。

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.