Tumor derived exosomal DDAH1 promotes lung aging and metastasis

Extracellular vesicles can remodel the premetastatic microenvironment of target organs by packaging various bioactive substances (including proteins and small RNA molecules) to promote tumor development and metastasis. DDAH1 is an asymmetric dimethylarginine hydrolase, which catalyzes the hydrolysis of ADMA to nitric oxide and citrulline to promote tumor development and angiogenesis. However, the role of DDAH1 carried by tumor-derived small extracellular vesicles in lung metastasis has not been reported. In this study, we revealed that tumor-derived small extracellular vesicles carry DDAH1 and promote its accumulation in the lung, facilitating the formation of the senescent matrix microenvironment in the lung and thereby affecting tumor metastasis. To study the effect of breast cancer small extracellular vesicles (EVs) derived DDAH1 on the lung of mice, we constructed an orthotopic breast cancer bearing mouse model. 4T1 and 4T1/DDAH1 KO cells were subcutaneously injected into the fourth pair of mammary glands of mice, respectively. After 5 weeks, the mice were sacrificed and the lungs were removed for preparation of single cell suspension for scRNA Seq.