1. Tumor perivascular cell-derived extracellular vesicles promote angiogenesis via the Gas6/Axl pathway
- Author
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Mingqun Liu, Xiangning Liu, Wen-Cai Ye, Yong Li, Qi Qi, Dandan Huang, Qing Wen, Lijuan Deng, Tongzheng Liu, Geni Ye, Maohua Huang, Yanping Ma, Dong-Mei Zhang, and Minfeng Chen
- Subjects
Cancer Research ,Cell Survival ,Perivascular Epithelioid Cell Neoplasms ,Angiogenesis ,Chorioallantoic Membrane ,Neovascularization ,Extracellular Vesicles ,Mice ,Cell Movement ,In vivo ,Proto-Oncogene Proteins ,Human Umbilical Vein Endothelial Cells ,medicine ,Animals ,Humans ,Neoplasm Invasiveness ,Aorta ,Cell Proliferation ,Tube formation ,Neovascularization, Pathologic ,GAS6 ,Chemistry ,Receptor Protein-Tyrosine Kinases ,Axl Receptor Tyrosine Kinase ,Rats ,Gene Expression Regulation, Neoplastic ,Oncology ,Tumor progression ,Cancer research ,Intercellular Signaling Peptides and Proteins ,Signal transduction ,medicine.symptom ,Colorectal Neoplasms ,Chickens ,Ex vivo - Abstract
Aberrant angiogenesis is a hallmark of cancer and is critically associated with tumor progression. Perivascular cells are essential components of blood vessels, and the role of tumor perivascular cell-derived extracellular vesicles (TPC-EVs) in angiogenesis remains elusive. In the present study, using genetic mouse models and pharmacological inhibitors, we found that ablation of perivascular cells inhibited angiogenesis in allografted colorectal cancer tumors. Further studies demonstrated that TPC-EVs promoted the proliferation, migration, invasion, viability, and tube formation of HUVECs. They also facilitated vessel spouting in rat aortic rings and induced neovascularization in chick chorioallantoic membranes (CAMs). Silencing of Gas6 or blockade of the Axl pathway suppressed TPC-EV-induced angiogenesis in vitro and ex vivo. Moreover, inhibition of the Gas6/Axl signaling pathway impaired TPC-EV-mediated angiogenesis in vivo. Our findings present a deeper insight into the biological functions of TPCs and TPC-EVs in tumor angiogenesis and demonstrate that TPC-EV-derived Gas6 could be an attractive and innovative regulator of tumor angiogenesis.
- Published
- 2022
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