Macrophage-mediated transfer of cancer-derived components to stromal cells contributes to establishment of a pro-tumor microenvironment.

摘要: Tumor-derived extracellular vesicles (TEVs) secreted into the blood create a pre-metastatic niche in distant organs; however, it is unclear how TEVs are delivered and they affect stromal cells tumor microenvironment. Tumor-associated macrophages (TAMs) have pivotal roles cancer progression by interacting with other cells. Here, we report novel function of TAMs: delivery transmission TEV contents. TEV-incorporating (TEV-MΦs) showed increased invasiveness were disseminated widely. Upon contact host (peritoneal mesothelial (PMCs), fibroblasts, endothelial cells), TEV-MΦs released membrane blebs containing TEVs, process dependent upon localized activation caspase-3 MΦs. Scattered incorporated cells, leading to transfer cancer-derived RNA proteins such as TGF-β, activated Src, Wnt3, HIF1α. TEV-MΦ-secreted components contributed myofibroblastic changes recipient MΦs penetrated deep parenchyma stomach TEV-injected mice, transmitted PMCs lining surface; this induced undergo mesothelial-mesenchymal transition. infiltrated gastric wall created niche, thereby promoting invasion. Depletion prevented these events. Moreover, pro-metastatic niche. Taken together, results suggest for surrounding induction pro-tumor microenvironment via an increase number CAF-like