Laboratory of the Molecular Biology of Cancer, Centre of New Technologies, University of Warsaw, 00-927 Warsaw, Poland.
Laboratory of Stem Cells, Tissue Development and Regeneration, Centre of New Technologies, University of Warsaw, 00-927 Warsaw, Poland.
Int J Mol Sci. 2021 Dec 23;23(1):140. doi: 10.3390/ijms23010140.
Head and neck squamous cell carcinoma (HNSCC) is an aggressive tumor with a poor prognosis due to late diagnosis and loco-regional metastasis. Partial or more complete epithelial-mesenchymal transition (EMT) plays a role in tumor progression; however, it remains a challenge to observe the EMT in vivo, due to its transient nature. Here, we developed a novel catulin promoter-based reporter system that allows us to isolate and characterize in vivo a small fraction of invasive cancer cells. The analyses of tumors revealed that Catulin-green fluorescent protein (GFP)-positive cells were enriched in clusters of cells at the tumor invasion front. A functional genomic study unveiled genes involved in cellular movement and invasion providing a molecular profile of HNSCC invasive cells. This profile overlapped partially with the expression of signature genes related to the partial EMT available from the single cell analysis of human HNSCC specimens, highlighting the relevance of our data to the clinical disease progression state. Interestingly, we also observed upregulations of genes involved in axonal guidance-L1 cell adhesion molecule (), neuropilin-1, semaphorins, and ephrins, indicating potential interactions of cancer cells and neuronal components of the stroma. Taken together, our data indicated that the catulin reporter system marked a population of invasive HNSCC cells with a molecular profile associated with cancer invasion.
头颈部鳞状细胞癌（HNSCC）是一种侵袭性肿瘤，由于诊断较晚和局部转移，预后较差。部分或更完全的上皮-间充质转化（EMT）在肿瘤进展中起作用；然而，由于其短暂的性质，观察体内 EMT 仍然是一个挑战。在这里，我们开发了一种新型的角蛋白启动子报告系统，使我们能够分离和鉴定体内少量侵袭性癌细胞。对肿瘤的分析表明，Catulin-绿色荧光蛋白（GFP）阳性细胞在肿瘤侵袭前沿的细胞簇中富集。功能基因组研究揭示了参与细胞运动和侵袭的基因，为 HNSCC 侵袭细胞提供了分子特征。该特征与来自人类 HNSCC 标本单细胞分析的部分 EMT 相关特征基因的表达部分重叠，突出了我们的数据与临床疾病进展状态的相关性。有趣的是，我们还观察到参与轴突导向-L1 细胞黏附分子（）、神经纤毛蛋白-1、神经鞘磷脂和 Ephrins 的基因上调，表明癌细胞与基质的神经元成分之间存在潜在的相互作用。总之，我们的数据表明，角蛋白报告系统标记了具有与癌症侵袭相关分子特征的侵袭性 HNSCC 细胞群体。
