Department of Otorhinolaryngology, Ruijin Hospital Lu Wan Branch, Shanghai Jiao Tong University School of Medicine, Shanghai, 200020, China.
Department of Laboratory Diagnostics, Changhai Hospital, Naval Medical University, Shanghai, 200433, China.
BMC Cancer. 2023 Nov 22;23(1):1135. doi: 10.1186/s12885-023-11630-7.
Most patients diagnosed with head and neck tumor will present with locally advanced disease, requiring multimodality therapy. Bone marrow-derived mesenchymal stromal cells (BMSCs) respond to a variety of tumor cell-derived signals, such as inflammatory cytokines and growth factors. As a result, the inflammatory tumor microenvironment may lead to the recruitment of BMSCs. Whether BMSCs in the tumor environment are more likely to promote tumor growth or tumor suppression is still controversial. We aimed to determine whether microRNA-21(miR-21) would play a vital role in HNSCC induced transition of human bone marrow mesenchymal stem cells (hBMSCs) to cancer-associated fibroblasts (CAFs).
In this study, we used electron microscope to observed exosomes collected from human tissue and two cell lines. We co-cultured hBMSCs with exosomes from FaDu and Cal-27 cells with miR-21 inhibited or not, then assessed cell cycle changes of hBMSCs with flow cytometry and determined expression level of α-SMA and FAP through qRT-PCR and Western blot.
We observed an up-regulation of miR-21 expression in HNSCC tissue and FaDu and Cal-27 cells. Importantly, the exosomes derived from both cells induced CAFs-like characteristics in hBMSCs. while treatment with a miR-21 inhibitor effectively suppressed the transition of hBMSCs to CAFs and reversed the changes in the cell cycle distribution. This suggests that miR-21 plays a crucial role in facilitating the transition of hBMSCs to CAFs and modulating the cell cycle dynamics.
Our findings highlight the significance of miR-21 in mediating the communication between HNSCC cells and hBMSCs through exosomes, leading to the promotion of CAFs-like features and alterations in the cell cycle of hBMSCs.
大多数诊断为头颈部肿瘤的患者将表现为局部晚期疾病，需要多模态治疗。骨髓间充质基质细胞（BMSCs）对多种肿瘤细胞衍生的信号（如炎症细胞因子和生长因子）作出反应。因此，炎症性肿瘤微环境可能导致 BMSC 的募集。肿瘤环境中的 BMSC 是否更有可能促进肿瘤生长或肿瘤抑制仍存在争议。我们旨在确定 microRNA-21（miR-21）是否会在头颈部鳞状细胞癌（HNSCC）诱导人骨髓间充质干细胞（hBMSCs）向癌相关成纤维细胞（CAFs）的转变中发挥重要作用。
在这项研究中，我们使用电子显微镜观察了从人组织和两个细胞系中收集的外泌体。我们将 hBMSCs 与 FaDu 和 Cal-27 细胞来源的外泌体共培养，其中 miR-21 被抑制或未被抑制，然后通过流式细胞术评估 hBMSCs 的细胞周期变化，并通过 qRT-PCR 和 Western blot 确定α-SMA 和 FAP 的表达水平。
我们观察到 HNSCC 组织和 FaDu 和 Cal-27 细胞中 miR-21 表达上调。重要的是，来自这两种细胞的外泌体诱导 hBMSCs 向 CAFs 样特征转变。而用 miR-21 抑制剂处理可有效抑制 hBMSCs 向 CAFs 的转变，并逆转细胞周期分布的变化。这表明 miR-21 在促进 hBMSCs 向 CAFs 的转变以及调节细胞周期动力学中起着关键作用。
我们的研究结果强调了 miR-21 在通过外泌体介导 HNSCC 细胞与 hBMSCs 之间通讯中的重要性，导致 CAFs 样特征的促进和 hBMSCs 细胞周期的改变。
