Department of Orthopaedic Surgery, The Affiliated Hospital of Qingdao University, 59 Haier Road, Qingdao, 266061, China.
Department of Obstetrics and Gynaecology, The Affiliated Hospital of Qingdao University, Qingdao, China.
Stem Cell Res Ther. 2019 Jun 13;10(1):168. doi: 10.1186/s13287-019-1280-3.
Spinal metastasis is a major challenge in patients with advanced lung cancer, but the mechanisms in the organotropism of metastasis are still unclear. Adipose-derived mesenchymal stem cells (ADSCs) exhibit cancer-promoting properties that influence the tumour microenvironment; however, there is no research on ADSCs from epidural fat thus far.
In this study, we isolated and identified ADSCs from epidural adipose tissue for the first time. We examined the activation of epidural ADSCs treated with lung cancer cell-conditioned medium by immunohistochemistry, western blot and qRT-PCR assays. The expression of interleukin (IL)-6 family cytokines in the supernatants of ADSCs were evaluated by enzyme-linked immunosorbent assay. The effects of epidural ADSCs on the growth and invasion of lung cancer cells were evaluated with the CCK-8 and Transwell assays. The expression of signal transducer and activator of transcription 3 (STAT3), matrix metalloprotease and epithelial-mesenchymal transition markers were measured by western blot assays.
Our results showed that ADSCs treated with lung cancer cell-conditioned medium expressed higher levels of the myofibroblast marker α-smooth muscle actin and fibroblast activation protein than ADSCs cultured alone. Then, we found that lung cancer cells induced ADSCs to secrete high levels of IL-6 family cytokines and activate the STAT3 signalling pathway. Moreover, activated epidural ADSCs exhibited the ability to promote lung cancer cell proliferation and invasion by elevating matrix metalloprotease expression and epithelial-mesenchymal transition in cancer cells. Furthermore, blocking IL-6 can counteract the differentiation and tumour-promoting effects of ADSCs.
Our results suggest that ADSCs respond to lung cancer cells and are involved in the crosstalk between primary tumours and pre-metastatic niches in epidural fat.
脊柱转移是晚期肺癌患者的主要挑战，但转移的器官趋向性机制仍不清楚。脂肪来源的间充质干细胞（ADSCs）具有促进肿瘤的特性，影响肿瘤微环境；然而，目前还没有关于硬膜外脂肪来源的 ADSCs 的研究。
本研究首次从硬膜外脂肪组织中分离和鉴定 ADSCs。我们通过免疫组织化学、western blot 和 qRT-PCR 检测了肺癌细胞条件培养基处理的硬膜外 ADSCs 的激活情况。通过酶联免疫吸附试验评估 ADSCs 上清液中白细胞介素（IL）-6 家族细胞因子的表达。用 CCK-8 和 Transwell 检测评估硬膜外 ADSCs 对肺癌细胞生长和侵袭的影响。通过 western blot 检测测量信号转导和转录激活因子 3（STAT3）、基质金属蛋白酶和上皮间质转化标志物的表达。
我们的结果表明，肺癌细胞条件培养基处理的 ADSCs 表达的肌成纤维细胞标志物α-平滑肌肌动蛋白和成纤维细胞激活蛋白比单独培养的 ADSCs 更高。然后，我们发现肺癌细胞诱导 ADSCs 分泌高水平的 IL-6 家族细胞因子并激活 STAT3 信号通路。此外，激活的硬膜外 ADSCs 通过提高基质金属蛋白酶表达和上皮间质转化，表现出促进肺癌细胞增殖和侵袭的能力。此外，阻断 IL-6 可以抵消 ADSCs 的分化和促肿瘤作用。
我们的结果表明，ADSCs 对肺癌细胞有反应，并参与原发性肿瘤和硬膜外脂肪中前转移龛之间的串扰。
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