Steinbichler T B, Savic D, Dejaco D, Romani A, Kofler B, Skvortsova I I, Riechelmann H, Dudas J
Department of Otorhinolaryngology, Head and Neck Surgery, Medical University of Innsbruck, Anichstr.35, A-6020, Innsbruck, Austria.
Department of Radiation Oncology, Medical University of Innsbruck, Anichstr.35, A-6020, Innsbruck, Austria.
Cancer Microenviron. 2019 Dec;12(2-3):67-76. doi: 10.1007/s12307-019-00228-y. Epub 2019 Jul 11.
Epithelial mesenchymal crosstalk (EMC) describes the interaction of the tumor stroma and associated fibroblasts with epithelial cancer cells. In this study we analysed the effects of EMC on head and neck cancer cells. In tumor cell lines EMC was induced using media conditioned from a mix-culture of cancer cells and fibroblasts. Cell proliferation and chemotherapy response were assessed using direct cell counting. Flow cytometry, immunohistochemistry of markers of epithelial-mesenchymal transition (EMT) and subsequent TissueFaxs™ acquisition and quantification and western blot analysis were performed. Holotomographic microscopy imaging was used to visualize the effects of EMC on Cisplatin response of SCC-25 cells. EMC induced a hybrid epithelial-mesenchymal phenotype in SCC-25 cells with co-expression of vimentin and cytokeratin. This hybrid phenotype was associated with chemotherapy resistance and increased proliferation of the cells. The EMC conditioned medium led to an activation of the IL-6/STAT3 pathway with subsequent phosphorylation of STAT3. EMC induced a hybrid epithelial-mesenchymal phenotype in HNSCC cells accompanied by increased therapy resistance and cell proliferation. The IL-6/STAT3 pathway might be one of the major pathways involved in these EMC-related effects.
上皮-间质相互作用（EMC）描述了肿瘤基质及相关成纤维细胞与上皮癌细胞之间的相互作用。在本研究中，我们分析了EMC对头颈部癌细胞的影响。在肿瘤细胞系中，通过使用癌细胞与成纤维细胞混合培养的条件培养基来诱导EMC。使用直接细胞计数法评估细胞增殖和化疗反应。进行了流式细胞术、上皮-间质转化（EMT）标志物的免疫组织化学检测以及随后的TissueFaxs™采集和定量分析，还有蛋白质免疫印迹分析。使用全息断层显微镜成像来观察EMC对SCC-25细胞顺铂反应的影响。EMC在SCC-25细胞中诱导了一种波形蛋白和细胞角蛋白共表达的混合上皮-间质表型。这种混合表型与化疗耐药性及细胞增殖增加有关。EMC条件培养基导致IL-6/STAT3信号通路激活，随后STAT3发生磷酸化。EMC在头颈部鳞状细胞癌（HNSCC）细胞中诱导了一种混合上皮-间质表型，同时伴随着治疗耐药性增加和细胞增殖。IL-6/STAT3信号通路可能是参与这些与EMC相关效应的主要信号通路之一。
