Exosomal CD44 Cooperates with Integrin α6β4 to Support Organotropic Metastasis via Regulating Tumor Cell Motility and Target Host Cell Activation
Exosomal CD44 Cooperates with Integrin α6β4 to Support Organotropic Metastasis via Regulating Tumor Cell Motility and Target Host Cell Activation作者机构：Center for Single-Cell Omics School of Public Health Shanghai Jiao Tong University School of Medicine CAS Key Laboratory of Nutrition Metabolism and Food Safety Shanghai Institute of Nutrition and Health Chinese Academy of Sciences National Research Center for Translational Medicine Shanghai Jiao Tong University School of Medicine
出 版 物：《Engineering》 (工程(英文))
年 卷 期：2021年第7卷第10期
页 面：1413-1423页
核心收录：
学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
基 金：sponsored by grants from the National Natural Science Foundation of China (81803269 and 81427805) the Science and Technology Commission of Shanghai Municipality (18YF1412100 and 2019Y0150) the National Key Research and Development Program of China (2018YFC2000700) the Key Research Program of the Chinese Academy of Sciences (ZDRW-ZS-2017-1) Shanghai Municipality Health Commission (GWV-10.2-YQ17 and 2019Y0150)
主 题：Pancreatic cancer Organotropic metastasis Exosomes Pre-metastatic niche CD44
摘 要：Rapid metastasis to vital organs such as the lung,liver,and brain is responsible for the vast majority of pancreatic cancer *** metastasis of pancreatic cancer accounts for the high mortality rate in *** derived from pancreatic cancer cells tend to be enriched in proteins that are anchored to the cell membrane,supporting the reprogramming of the tumor microenvironment and the progression of distant metastatic *** the first time,our study has demonstrated that cluster of differentiation 44(CD44),a transmembrane glycoprotein delivered by exosomes,is involved in the metastatic process of pancreatic ***,CD44 was found to interact with integrin α6β4 to form a complex,thereby remodeling intracellular skeleton proteins,and to promote tumor cell motility through the activation of the Src and Ras signaling ***,we also demonstrated that the CD44-α6β4 complex can be delivered to the target region via the paracrine effects of *** selective uptake of CD44-competent tumor exosomes by liver cells activated fibrotic pathways and generated a pre-metastatic niche by stimulating the cytokines,proinflammatory factors,and growth factors that ultimately support tumor *** results suggest the potential application of exosomal CD44 as a biomarker for the clinical diagnosis of and therapy for pancreatic cancer.
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