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Abstract：
Tissue clearing is one of the most powerful strategies for a comprehensive analysis of disease progression. Here, we established an integrated pipeline that combines tissue clearing, 3D imaging, and machine learning and applied to a mouse tumour model of experimental lung metastasis using human lung adenocarcinoma A549 cells. This pipeline provided the spatial information of the tumour microenvironment. We further explored the role of transforming growth factor-β (TGF-β) in cancer metastasis. TGF-β-stimulated cancer cells enhanced metastatic colonization of unstimulated-cancer cells in vivo when both cells were mixed. RNA-sequencing analysis showed that expression of the genes related to coagulation and inflammation were up-regulated in TGF-β-stimulated cancer cells. Further, whole-organ analysis revealed accumulation of platelets or macrophages with TGF-β-stimulated cancer cells, suggesting that TGF-β might promote remodelling of the tumour microenvironment, enhancing the colonization of cancer cells. Hence, our integrated pipeline for 3D profiling will help the understanding of the tumour microenvironment.
摘要：
组织清除是全面分析疾病进展的最有力策略之一。这里,我们建立了一个结合组织清理的综合管道，3D成像,和机器学习，并应用于使用人肺腺癌A549细胞的实验性肺转移的小鼠肿瘤模型。该管道提供了肿瘤微环境的空间信息。我们进一步探讨了转化生长因子-β（TGF-β）在癌症转移中的作用。当两种细胞混合时，TGF-β刺激的癌细胞增强了未刺激的癌细胞在体内的转移定植。RNA测序分析表明，与凝血和炎症相关的基因在TGF-β刺激的癌细胞中表达上调。Further,全器官分析显示血小板或巨噬细胞与TGF-β刺激的癌细胞的积累，这表明TGF-β可能促进肿瘤微环境的重塑，增强癌细胞的定植。因此，我们的3D分析集成管道将有助于了解肿瘤微环境。
