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癌相关成纤维细胞衍生的外泌体 miR-382-5p 促进口腔鳞状细胞癌的迁移和侵袭。

Cancer‑associated fibroblast‑derived exosomal miR‑382‑5p promotes the migration and invasion of oral squamous cell carcinoma.

机构信息

School of Stomatology, Shandong University, Jinan, Shandong 250100, P.R. China.

Department of Stomatology, Liaocheng People's Hospital, Medical School of Liaocheng University, Liaocheng, Shandong 252000, P.R. China.

出版信息

Oncol Rep. 2019 Oct;42(4):1319-1328. doi: 10.3892/or.2019.7255. Epub 2019 Jul 30.

Abstract

Oral squamous cell carcinoma (OSCC), with high potential for metastasis, is the most common malignant tumor of the head and neck. Cancer‑associated fibroblasts (CAFs) are the main stromal cells in the microenvironment and aggravate tumor progression. However, whether CAFs are associated with the progression of OSCC remains unknown and the underlying mechanism remains unclear. In the present study, the role of CAFs in mediating OSCC cell migration and invasion was investigated, and the participation of exosomal miR‑382‑5p in this process was elucidated. In this study, according to the α‑SMA staining with immunohistochemistry, 47 OSCC patients were divided into CAFs‑rich and CAFs poor groups, and association of CAF density and clinicopathologic features of the OSCC patients were analyzed with Pearson χ2 test. Transwell assay was used for evaluating cell migration and invasion ability of OSCC cells after being co‑cultured with NFs or CAFs, or after added exosomes. qPCR was used to detect the expression of miR‑382‑5p. Western blot analysis was used to measure the expression of migration and invasion‑associated proteins. In the present study, the CAF density in tumor tissues was found to be relevant to OSCC lymph node metastasis and TNM stage. Furthermore, we revealed that miR‑382‑5p was overexpressed in CAFs compared with that in fibroblasts of adjacent normal tissue and miR‑382‑5p overexpression was responsible for OSCC cell migration and invasion. Finally, we demonstrated that CAF‑derived exosomes transported miR‑382‑5p to OSCC cells. The present study confirmed a new mechanism of CAF‑facilitated OSCC progression and may be beneficial for identifying new cancer therapeutic targets.

摘要

口腔鳞状细胞癌(OSCC)具有较高的转移潜能,是头颈部最常见的恶性肿瘤。癌症相关成纤维细胞(CAFs)是肿瘤微环境中的主要基质细胞,加剧肿瘤的进展。然而,CAFs 是否与 OSCC 的进展有关尚不清楚,其潜在机制仍不清楚。在本研究中,研究了 CAFs 介导体外培养的 OSCC 细胞迁移和侵袭的作用,并阐明了外泌体 miR-382-5p 在此过程中的参与。在本研究中,根据免疫组织化学的 α-SMA 染色,将 47 例 OSCC 患者分为 CAFs 丰富组和 CAFs 缺乏组,采用 Pearson χ2检验分析 CAF 密度与 OSCC 患者临床病理特征的关系。采用 Transwell 实验检测 OSCC 细胞与 NF 或 CAFs 共培养或添加外泌体后迁移和侵袭能力的变化。采用 qPCR 检测 miR-382-5p 的表达。采用 Western blot 分析检测迁移和侵袭相关蛋白的表达。本研究发现肿瘤组织中 CAF 密度与 OSCC 淋巴结转移和 TNM 分期有关。此外,我们揭示了与邻近正常组织的成纤维细胞相比,CAFs 中 miR-382-5p 表达上调,miR-382-5p 过表达是导致 OSCC 细胞迁移和侵袭的原因。最后,我们证明了 CAF 衍生的外泌体将 miR-382-5p 转运至 OSCC 细胞。本研究证实了 CAF 促进 OSCC 进展的新机制,可能有助于确定新的癌症治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/209c/6718099/bc6942212066/or-42-04-1319-g00.jpg

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