Annexin A1 Released in Extracellular Vesicles by Pancreatic Cancer Cells Activates Components of the Tumor Microenvironment, through Interaction with the Formyl-Peptide Receptors.
Annexin A1 Released in Extracellular Vesicles by Pancreatic Cancer Cells Activates Components of the Tumor Microenvironment, through Interaction with the Formyl-Peptide Receptors.
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DOI：
10.3390/cells9122719
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发表时间：
2020-12-18
期刊：
影响因子：
6
通讯作者：
Petrella A
中科院分区：
文献类型：
--
作者：
Novizio N;Belvedere R;Pessolano E;Tosco A;Porta A;Perretti M;Campiglia P;Filippelli A;Petrella A
胰腺癌（PC）是世界上最具侵袭性的癌症之一。几种细胞外因子参与其发展和转移到远处器官。在PC中，蛋白质膜联蛋白A1（ANXA 1）似乎过表达，并可能被鉴定为致癌因子，也因为它是肿瘤衍生的细胞外囊泡（EV）的组分。事实上，已知这些微泡滋养肿瘤微环境。一旦我们评估了含有ANXA 1的EV对PC MIA PaCa-2细胞的自分泌作用及其促血管生成作用，我们就研究了ANXA 1对基质细胞如成纤维细胞和内皮细胞的旁分泌作用。关于成纤维细胞、细胞迁移/侵袭、细胞骨架重塑和特异性蛋白质标志物的不同表达的分析，在施用野生型多于ANXA 1敲除EV后评估细胞转换成肌成纤维细胞的所有特征。有趣的是，我们证明了ANXA 1-EVs复合物可以刺激甲酰肽受体（FPRs）激活的机制，触发成纤维细胞和内皮细胞上的间充质开关和细胞运动。因此，我们强调了ANXA 1/EVs-FPR轴在PC进展中作为相互交流肿瘤细胞-基质的媒介物的重要性，表明ANXA 1的特定潜在预后/诊断作用，无论是可溶性形式还是即使EV在PC中被捕获。
Pancreatic cancer (PC) is one of the most aggressive cancers in the world. Several extracellular factors are involved in its development and metastasis to distant organs. In PC, the protein Annexin A1 (ANXA1) appears to be overexpressed and may be identified as an oncogenic factor, also because it is a component in tumor-deriving extracellular vesicles (EVs). Indeed, these microvesicles are known to nourish the tumor microenvironment. Once we evaluated the autocrine role of ANXA1-containing EVs on PC MIA PaCa-2 cells and their pro-angiogenic action, we investigated the ANXA1 paracrine effect on stromal cells like fibroblasts and endothelial ones. Concerning the analysis of fibroblasts, cell migration/invasion, cytoskeleton remodeling, and the different expression of specific protein markers, all features of the cell switching into myofibroblasts, were assessed after administration of wild type more than ANXA1 Knock-Out EVs. Interestingly, we demonstrated a mechanism by which the ANXA1-EVs complex can stimulate the activation of formyl peptide receptors (FPRs), triggering mesenchymal switches and cell motility on both fibroblasts and endothelial cells. Therefore, we highlighted the importance of ANXA1/EVs-FPR axes in PC progression as a vehicle of intercommunication tumor cells-stroma, suggesting a specific potential prognostic/diagnostic role of ANXA1, whether in soluble form or even if EVs are captured in PC.
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影响因子：
4.6
作者：
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通讯作者：
Lyden D
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4.6
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