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肿瘤相关成纤维细胞衍生的外泌体通过 RIG-I/IFN-β 信号诱导食管鳞癌细胞的增殖和顺铂耐药。

Tumor-associated fibroblasts derived exosomes induce the proliferation and cisplatin resistance in esophageal squamous cell carcinoma cells through RIG-I/IFN-β signaling.

机构信息

Department of Cancer Radiotherapy, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China (Anhui Provincial Cancer Hospital), Hefei, Anhui, China.

Department of Gastroenterology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China.

出版信息

Bioengineered. 2022 May;13(5):12462-12474. doi: 10.1080/21655979.2022.2076008.

DOI:10.1080/21655979.2022.2076008
PMID:35587143
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9275880/
Abstract

Esophageal squamous cell carcinoma (ESCC) is a common type of malignant cancer. There is growing evidence suggesting that exosomes may participate in the cellular communication of tumor-associated fibroblasts (TAFs). However, the cisplatin resistance of TAF-derived exosomes to ESCC cells remains to be further studied. Exosomes were isolated from TAFs and characterized with Western blot and TEM assays. ESCC cell lines (TE-1 and KYSE-150) were incubated with TAFs-derived exosomes. To explore the biological function of TAF-derived exosomes in ESCC cell proliferation, apoptosis, and chemosensitivity, we conducted MTT assays and Flow Cytometry. The effects were also verified via Xenograft mice models. We found that TAFs-derived exosomes led to enhanced cell proliferation and reduced apoptosis of cells, accompanied by increased expression of RIG-I/IFN-β, and TAFs derived exosomes may affect the chemosensitivity to cisplatin via RIG-I/IFN-β signaling in ESCC. Taken together, ESCC cells could communicate with TAFs cells via TAFs-derived exosomes. Our findings might represent a novel mechanism involved in ESCC and may provide a potential biomarker for ESCC.

摘要

食管鳞状细胞癌(ESCC)是一种常见的恶性肿瘤。越来越多的证据表明,外泌体可能参与肿瘤相关成纤维细胞(TAFs)的细胞通讯。然而,TAF 衍生的外泌体对 ESCC 细胞的顺铂耐药性仍有待进一步研究。通过 Western blot 和 TEM 检测从 TAFs 中分离出外泌体并进行鉴定。将 ESCC 细胞系(TE-1 和 KYSE-150)与 TAF 衍生的外泌体孵育。为了探讨 TAF 衍生的外泌体在 ESCC 细胞增殖、凋亡和化疗敏感性中的生物学功能,我们进行了 MTT 检测和流式细胞术检测。还通过异种移植小鼠模型验证了这些作用。我们发现 TAFs 衍生的外泌体导致细胞增殖增强和凋亡减少,同时伴随着 RIG-I/IFN-β 的表达增加,TAFs 衍生的外泌体可能通过 RIG-I/IFN-β 信号通路影响 ESCC 对顺铂的化疗敏感性。总之,ESCC 细胞可以通过 TAFs 衍生的外泌体与 TAFs 细胞进行通讯。我们的发现可能代表了 ESCC 中涉及的一种新机制,并可能为 ESCC 提供一个潜在的生物标志物。

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