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肿瘤微环境中胰腺癌细胞与癌相关成纤维细胞间的外泌体 microRNAs 串扰。

Crosstalk between Pancreatic Cancer Cells and Cancer-Associated Fibroblasts in the Tumor Microenvironment Mediated by Exosomal MicroRNAs.

机构信息

Department of General Surgery, Peking University First Hospital, Beijing 100034, China.

出版信息

Int J Mol Sci. 2022 Aug 23;23(17):9512. doi: 10.3390/ijms23179512.

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant digestive tumors, characterized by a low rate of early diagnosis, strong invasiveness, and early metastasis. The abundant stromal cells, dense extracellular matrix, and lack of blood supply in PDAC limit the penetration of chemotherapeutic drugs, resulting in poor efficacy of the current treatment regimens. Cancer-associated fibroblasts (CAFs) are the major stromal cells in the tumor microenvironment. Tumor cells can secrete exosomes to promote the generation of activated CAFs, meanwhile exosomes secreted by CAFs help promote tumor progression. The aberrant expression of miRNAs in exosomes is involved in the interaction between tumor cells and CAFs, which provides the possibility for the application of exosomal miRNAs in the diagnosis and treatment of PDAC. The current article reviews the mechanism of exosomal miRNAs in the crosstalk between PDAC cells and CAFs in the tumor microenvironment, in order to improve the understanding of TME regulation and provide evidence for designing diagnostic and therapeutic targets against exosome miRNA in human PDAC.

摘要

胰腺导管腺癌(PDAC)是最恶性的消化肿瘤之一,其特点是早期诊断率低、侵袭性强、早期转移。PDAC 中丰富的基质细胞、密集的细胞外基质和缺乏血液供应限制了化疗药物的渗透,导致目前治疗方案的疗效不佳。癌相关成纤维细胞(CAFs)是肿瘤微环境中的主要基质细胞。肿瘤细胞可以分泌外泌体来促进激活的 CAFs 的产生,同时 CAFs 分泌的外泌体有助于促进肿瘤的进展。外泌体 miRNA 的异常表达参与了肿瘤细胞与 CAFs 之间的相互作用,为外泌体 miRNA 在 PDAC 的诊断和治疗中的应用提供了可能性。本文综述了外泌体 miRNA 在 PDAC 细胞与肿瘤微环境中的 CAFs 之间相互作用中的作用机制,以期提高对 TME 调控的认识,并为针对人类 PDAC 的外泌体 miRNA 设计诊断和治疗靶点提供依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3be/9455258/5989484ca8f5/ijms-23-09512-g001.jpg

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