Whole-organ analysis of TGF-β-mediated remodelling of the tumour microenvironment by tissue clearing.
Whole-organ analysis of TGF-β-mediated remodelling of the tumour microenvironment by tissue clearing.
复制标题
通过组织清除对 TGF-β 介导的肿瘤微环境重塑进行全器官分析。
DOI：
10.1038/s42003-021-01786-y
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发表时间：
2021-03-05
影响因子：
5.9
通讯作者：
Miyazono K
中科院分区：
文献类型：
--
作者：
Kubota SI;Takahashi K;Mano T;Matsumoto K;Katsumata T;Shi S;Tainaka K;Ueda HR;Ehata S;Miyazono K
组织清除是综合分析疾病进展的最有力策略之一。在这里，我们建立了一个集成的管道，结合了组织清除，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体内未刺激的癌细胞的转移定植。RNA测序分析显示，在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，全器官分析揭示了血小板或巨噬细胞与TGF-β刺激的癌细胞的积累，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，我们用于3D分析的集成管道将有助于了解肿瘤微环境。Shimei Kubota等人描述了一种用于定量全器官分析的管道，该管道结合了组织清除，3D成像和机器学习来分析肿瘤微环境。作者将其应用于小鼠肺肿瘤模型，并揭示了TGF-β在重塑有利于转移性侵袭的细胞微环境中的作用。
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. Shimpei Kubota et al. describe a pipeline for quantitative whole-organ analysis that that combines tissue clearing, 3D imaging, and machine learning for analysis of the tumour microenvironment. The authors apply this in a mouse model of lung tumour and reveal the role of TGF-β in remodelling the cellular microenvironment favouring metastatic invasion.
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影响因子：
6.6
作者：
Katsura A;Tamura Y;Hokari S;Harada M;Morikawa M;Sakurai T;Takahashi K;Mizutani A;Nishida J;Yokoyama Y;Morishita Y;Murakami T;Ehata S;Miyazono K;Koinuma D
通讯作者：
Koinuma D
影响因子：
64.8
作者：
Fischer KR;Durrans A;Lee S;Sheng J;Li F;Wong ST;Choi H;El Rayes T;Ryu S;Troeger J;Schwabe RF;Vahdat LT;Altorki NK;Mittal V;Gao D
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Gao D
影响因子：
50.3
作者：
Labelle M;Begum S;Hynes RO
通讯作者：
Hynes RO
影响因子：
64.8
作者：
Mariathasan S;Turley SJ;Nickles D;Castiglioni A;Yuen K;Wang Y;Kadel EE III;Koeppen H;Astarita JL;Cubas R;Jhunjhunwala S;Banchereau R;Yang Y;Guan Y;Chalouni C;Ziai J;Şenbabaoğlu Y;Santoro S;Sheinson D;Hung J;Giltnane JM;Pierce AA;Mesh K;Lianoglou S;Riegler J;Carano RAD;Eriksson P;Höglund M;Somarriba L;Halligan DL;van der Heijden MS;Loriot Y;Rosenberg JE;Fong L;Mellman I;Chen DS;Green M;Derleth C;Fine GD;Hegde PS;Bourgon R;Powles T
通讯作者：
Powles T
影响因子：
16.6
作者：
Cuccarese MF;Dubach JM;Pfirschke C;Engblom C;Garris C;Miller MA;Pittet MJ;Weissleder R
通讯作者：
Weissleder R