Spatiotemporal quantification of metastatic tumour cell growth and distribution in lymph nodes by whole-mount tissue 3D imaging.
Spatiotemporal quantification of metastatic tumour cell growth and distribution in lymph nodes by whole-mount tissue 3D imaging.
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通过全组织 3D 成像对淋巴结中转移性肿瘤细胞的生长和分布进行时空定量。
DOI：
10.7150/ijbs.72552
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发表时间：
2022
影响因子：
9.2
通讯作者：
Zhang, Zhi-Gang
中科院分区：
文献类型：
--
作者：
Li, Jun;Xu, Chun-Jie;Tian, Guang-Ang;Li, Qing;Li, Dong-Xue;Yan, Fang;Zhou, Yao-Qi;Huang, Pei-Qi;Xie, Jia-Xuan;Wang, Xu;Jiang, Shu-Heng;Wang, Ya-Hui;Song, Jian;Zhang, Xue-Li;Yi, Shuang-Qin;Hu, Li-Peng;Xu, Qing;Li, Xiao-Wei;Zhang, Zhi-Gang
淋巴结（LN）是许多实体癌的常见转移部位。肿瘤细胞可以迁移到LN，进一步转移到远处器官，表明预后不良，需要不同的临床干预。目前用于检测临床淋巴结转移（LNM）的组织病理学诊断方法存在局限性，例如不完全可视化。为了在空间和时间尺度上获得转移性淋巴结的完整图像，我们使用了溶剂清除器官的最终3D成像（uDISCO）和3D快速免疫染色。将标记有EGFP的MC 38细胞注射到C57 BL/6小鼠的左足垫中。使用uDISCO方法清除从这些小鼠收获的引流淋巴结（DLN）。使用整体组织的3D成像来量化在不同时间点来自小鼠的DLN的各个区域中的转移性结直肠癌（CRC）细胞。确定了淋巴结中肿瘤细胞生长和分布的几个阶段：1）侵入淋巴管（LV）和血管（BV）; 2）扩散到LV和BV外进行增殖和扩增; 3）重新进入BV和传出淋巴管（ELV）进行进一步的远处转移。此外，这些数据表明，小鼠成纤维细胞（MFC）不仅可以促进肿瘤细胞的LNM，而且可以与肿瘤细胞一起转移到LN，从而为肿瘤细胞定植提供“土壤”。总之，整体组织的3D成像和LNM的时空分析可以共同构成提高临床LNM检测准确性的辅助方法。
Lymph nodes (LNs) are a common site of metastasis in many solid cancers. Tumour cells can migrate to LNs for further metastatic colonization of distant organs, indicating poor prognosis and requiring different clinical interventions. The histopathological diagnostic methods currently used to detect clinical lymph node metastasis (LNM) have limitations, such as incomplete visualization. To obtain a complete picture of metastatic LNs on the spatial and temporal scales, we used ultimate 3D imaging of solvent-cleared organs (uDISCO) and 3D rapid immunostaining. MC38 cells labelled with EGFP were injected into the left footpads of C57BL/6 mice. Draining lymph nodes (DLNs) harvested from these mice were cleared using the uDISCO method. Metastatic colorectal cancer (CRC) cells in various regions of DLNs from mice at different time points were quantified using 3D imaging of whole-mount tissue. Several stages of tumour cell growth and distribution in LNs were identified: 1) invasion of lymphatic vessels (LVs) and blood vessels (BVs); 2) dispersion outside LVs and BVs for proliferation and expansion; and 3) re-entry into BVs and efferent lymphatic vessels (ELVs) for further distant metastasis. Moreover, these data demonstrated that mouse fibroblast cells (MFCs) could not only promote LNM of tumour cells but also metastasize to LNs together with tumour cells, thus providing a “soil” for tumour cell colonization. In conclusion, 3D imaging of whole-mount tissue and spatiotemporal analysis of LNM may collectively constitute an auxiliary method to improve the accuracy of clinical LNM detection.
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影响因子：
2.4
作者：
Shin, Jung Ha;Bae, Jeong Hoon;Lee, Kyo-Young
通讯作者：
Lee, Kyo-Young
影响因子：
48
作者：
Pan, Chenchen;Cai, Ruiyao;Ertuerk, Ali
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Ertuerk, Ali
影响因子：
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作者：
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Kolacinska, A.
影响因子：
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通讯作者：
Ohtani, Yuko
影响因子：
30.5
作者：
Reynoso, Glennys V.;Weisberg, Andrea S.;Hickman, Heather D.
通讯作者：
Hickman, Heather D.