Department of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Department of Systems Pharmacology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Commun Biol. 2021 Mar 5;4(1):294. doi: 10.1038/s42003-021-01786-y.
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.
组织透明化是全面分析疾病进展最有效的策略之一。在这里，我们建立了一个集成的工作流程，结合组织透明化、3D 成像和机器学习，并应用于使用人肺腺癌细胞 A549 的实验性肺转移小鼠肿瘤模型。该工作流程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受刺激的癌细胞在体内的转移定植。RNA 测序分析显示，TGF-β 刺激的癌细胞中与凝血和炎症相关的基因表达上调。此外，整体器官分析显示，血小板或巨噬细胞在 TGF-β 刺激的癌细胞中积累，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 分析集成工作流程将有助于理解肿瘤微环境。
