a Department of Breast and Thyroid Surgery , Renmin Hospital of Wuhan University , Wuhan , Hubei , P. R. China.
b Department of Clinical Laboratory , Renmin Hospital of Wuhan University , Wuhan , Hubei , P. R. China.
Adipocyte. 2019 Dec;8(1):31-45. doi: 10.1080/21623945.2018.1551688. Epub 2018 Dec 11.
Cancer-secreted exosomes are emerging mediators of cancer-associated cachexia. Here, we show that miR-155 secreted by breast cancer cells is a potent role on the catabolism of adipocytes and muscle cells through targeting the PPARγ. After cocultivated with mature adipocytes or C2C12, tumour cells exhibit an aggressive phenotype via inducing epithelial-mesenchymal transition while breast cancer-derived exosomes increased catabolism and release the metabolites in adipocytes and muscle cells. In adipocytes, cancer cell-secreted miR-155 promotes beige/brown differentiation and remodel metabolism in resident adipocytes by downregulating the PPARγ expression, but does not significantly affect biological conversion in C2C12. Likewise, propranolol ameliorates tumour exosomes-associated cachectic wasting through upregulating the PPARγ expression. In summary, we have demonstrated that the transfer of miR-155 from exosomes acts as an oncogenic signal reprograming systemic energy metabolism and leading to cancer-associated cachexia in breast cancer.
癌症来源的外泌体正在成为癌症相关性恶病质的新介质。在这里，我们表明乳腺癌细胞分泌的 miR-155 通过靶向 PPARγ 对脂肪细胞和肌肉细胞的分解代谢起重要作用。与成熟脂肪细胞或 C2C12 共培养后，肿瘤细胞通过诱导上皮-间充质转化表现出侵袭性表型，而乳腺癌来源的外泌体增加了脂肪细胞和肌肉细胞的分解代谢并释放代谢物。在脂肪细胞中，癌细胞分泌的 miR-155 通过下调 PPARγ 的表达促进米色/棕色分化和重塑驻留脂肪细胞的代谢，但对 C2C12 中的生物学转化没有显著影响。同样，普萘洛尔通过上调 PPARγ 的表达改善肿瘤外泌体相关恶病质消耗。总之，我们已经证明，miR-155 从外泌体中的转移充当致癌信号，重新编程全身能量代谢，导致乳腺癌相关性恶病质。
