转化生长因子β（TGFβ）是癌症患者肿瘤来源小细胞外囊泡（TEX）的主要成分。 TGFβ+ TEX利用的机制，促进肿瘤微环境（TME）中的肿瘤生长和亲肿瘤活动仍大多数未知。乳腺癌细胞系产生的TEX携带TGFβ和促血管生成蛋白。TGFβ+ TEX刺激巨噬细胞趋化，没有明显的M1 / M2表型转变，并重编程原始人类巨噬细胞为具有上调促血管生成因素和功能的亲血管生成表型。在鼠基底膜提取物插件模型中，TGFβ+ TEX促进了巨噬细胞浸润和血管化（p<0.001），使用TGFβ配体陷阱mRER（p<0.001）阻止了这一过程。将TGFβ+ TEX注射给接受4-硝基喹啉-1-氧化物（4-NQO）驱动的口腔癌变的小鼠，促进了肿瘤血管生成(p <0.05)、 TME中类M2巨噬细胞的浸润 (p<0.05) 和最终的肿瘤进展（p<0.05）。使用mRER抑制TEX中的TGFβ信号传导，可以改善这些亲肿瘤活动。沉默TGFβ成为抑制HNSCC中TEX亲血管生成功能的关键一步。 ©2022 The Authors。由Wiley Periodicals, LLC代表国际细胞外囊泡学会出版的《细胞外囊泡杂志》。

Transforming growth factor β (TGFβ) is a major component of tumor-derived small extracellular vesicles (TEX) in cancer patients. Mechanisms utilized by TGFβ+ TEX to promote tumor growth and pro-tumor activities in the tumor microenvironment (TME) are largely unknown. TEX produced by head and neck squamous cell carcinoma (HNSCC) cell lines carried TGFβ and angiogenesis-promoting proteins. TGFβ+ TEX stimulated macrophage chemotaxis without a notable M1/M2 phenotype shift and reprogrammed primary human macrophages to a pro-angiogenic phenotype characterized by the upregulation of pro-angiogenic factors and functions. In a murine basement membrane extract plug model, TGFβ+ TEX promoted macrophage infiltration and vascularization (p < 0.001), which was blocked by using the TGFβ ligand trap mRER (p < 0.001). TGFβ+ TEX injected into mice undergoing the 4-nitroquinoline-1-oxide (4-NQO)-driven oral carcinogenesis promoted tumor angiogenesis (p < 0.05), infiltration of M2-like macrophages in the TME (p < 0.05) and ultimately tumor progression (p < 0.05). Inhibition of TGFβ signaling in TEX with mRER ameliorated these pro-tumor activities. Silencing of TGFβ emerges as a critical step in suppressing pro-angiogenic functions of TEX in HNSCC.© 2022 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles.