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Spatiotemporal quantification of metastatic tumour cell growth and distribution in lymph nodes by whole-mount tissue 3D imaging
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...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9274482/ https://www.ncbi.nlm.nih.gov/pubmed/35844788 http://dx.doi.org/10.7150/ijbs.72552 |
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author | 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 |
author_facet | 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 |
author_sort | Li, Jun |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9274482 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-92744822022-07-15 Spatiotemporal quantification of metastatic tumour cell growth and distribution in lymph nodes by whole-mount tissue 3D imaging 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 Int J Biol Sci Research Paper 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. Ivyspring International Publisher 2022-06-13 /pmc/articles/PMC9274482/ /pubmed/35844788 http://dx.doi.org/10.7150/ijbs.72552 Text en © The author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. |
spellingShingle | Research Paper 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 Spatiotemporal quantification of metastatic tumour cell growth and distribution in lymph nodes by whole-mount tissue 3D imaging |
title | Spatiotemporal quantification of metastatic tumour cell growth and distribution in lymph nodes by whole-mount tissue 3D imaging |
title_full | Spatiotemporal quantification of metastatic tumour cell growth and distribution in lymph nodes by whole-mount tissue 3D imaging |
title_fullStr | Spatiotemporal quantification of metastatic tumour cell growth and distribution in lymph nodes by whole-mount tissue 3D imaging |
title_full_unstemmed | Spatiotemporal quantification of metastatic tumour cell growth and distribution in lymph nodes by whole-mount tissue 3D imaging |
title_short | Spatiotemporal quantification of metastatic tumour cell growth and distribution in lymph nodes by whole-mount tissue 3D imaging |
title_sort | spatiotemporal quantification of metastatic tumour cell growth and distribution in lymph nodes by whole-mount tissue 3d imaging |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9274482/ https://www.ncbi.nlm.nih.gov/pubmed/35844788 http://dx.doi.org/10.7150/ijbs.72552 |
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