Lymphatic system is the mainstream for breast cancer dissemination and metastasis revealed by single-cell lineage tracing
Abstract Cancer metastasis is the primary cause of cancer-related death, yet the forces that drive cancer cells through various steps and different routes to distinct target organs/tissues remain elusive. In this study, we applied a barcoding system based single-cell lineage tracing approach to stud...
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| Format: | Article |
| Language: | English |
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BMC
2025-03-01
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| Series: | Molecular Cancer |
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| Online Access: | https://doi.org/10.1186/s12943-025-02279-w |
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| author | Kai Miao Aiping Zhang Xiaodan Yang Yipeng Zhang Anqi Lin Lijian Wang Xin Zhang Heng Sun Jun Xu Jingyao Zhang Yuzhao Feng Fangyuan Shao Sen Guo Zhihui Weng Peng Luo Dong Wang Shuai Gao Xiao-Yang Zhao Xiaoling Xu Chu-Xia Deng |
| author_facet | Kai Miao Aiping Zhang Xiaodan Yang Yipeng Zhang Anqi Lin Lijian Wang Xin Zhang Heng Sun Jun Xu Jingyao Zhang Yuzhao Feng Fangyuan Shao Sen Guo Zhihui Weng Peng Luo Dong Wang Shuai Gao Xiao-Yang Zhao Xiaoling Xu Chu-Xia Deng |
| author_sort | Kai Miao |
| collection | DOAJ |
| description | Abstract Cancer metastasis is the primary cause of cancer-related death, yet the forces that drive cancer cells through various steps and different routes to distinct target organs/tissues remain elusive. In this study, we applied a barcoding system based single-cell lineage tracing approach to study the metastasis rate and route of breast cancer cells and their interactions with the tumor microenvironment (TME) during metastasis. The results indicate that only a small fraction of cells, accounting for fewer than 3% of total barcodes, can intravasate from the primary site into the blood circulation, whereas more cells disseminate through the lymphatic system to different organs. Tumor cells derived from the same progenitor cell exhibit different gene expression patterns in different soils, and the cancer cell-TME communication paradigm varies significantly between primary and metastatic tumors. Furthermore, metastable cells require a prewired particular cytokine expression ability which may be specific for lymph metastasis route although the underlying mechanism requires further investigation. In summary, leveraging a single-cell lineage tracing system, we demonstrate that the crosstalk between tumor cells and the TME is the driving force controlling the preferential metastatic fate of cancer cells through the lymphatic system. Graphical Abstract |
| format | Article |
| id | doaj-art-d18770ecb0694eb2ba25850feeb1794d |
| institution | DOAJ |
| issn | 1476-4598 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Cancer |
| spelling | doaj-art-d18770ecb0694eb2ba25850feeb1794d2025-08-20T03:01:34ZengBMCMolecular Cancer1476-45982025-03-0124111010.1186/s12943-025-02279-wLymphatic system is the mainstream for breast cancer dissemination and metastasis revealed by single-cell lineage tracingKai Miao0Aiping Zhang1Xiaodan Yang2Yipeng Zhang3Anqi Lin4Lijian Wang5Xin Zhang6Heng Sun7Jun Xu8Jingyao Zhang9Yuzhao Feng10Fangyuan Shao11Sen Guo12Zhihui Weng13Peng Luo14Dong Wang15Shuai Gao16Xiao-Yang Zhao17Xiaoling Xu18Chu-Xia Deng19Cancer Center, Faculty of Health Sciences, University of MacauCancer Center, Faculty of Health Sciences, University of MacauCancer Center, Faculty of Health Sciences, University of MacauCancer Center, Faculty of Health Sciences, University of MacauCancer Center, Faculty of Health Sciences, University of MacauCancer Center, Faculty of Health Sciences, University of MacauCancer Center, Faculty of Health Sciences, University of MacauCancer Center, Faculty of Health Sciences, University of MacauCancer Center, Faculty of Health Sciences, University of MacauKey Laboratory of Animal Genetics, Breeding and Reproduction of the MARA, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural UniversityCancer Center, Faculty of Health Sciences, University of MacauCancer Center, Faculty of Health Sciences, University of MacauCancer Center, Faculty of Health Sciences, University of MacauCancer Center, Faculty of Health Sciences, University of MacauCancer Center, Faculty of Health Sciences, University of MacauDepartment of Developmental Biology, State Key Laboratory of Organ Failure Research, School of Basic Medical Sciences, Southern Medical UniversityKey Laboratory of Animal Genetics, Breeding and Reproduction of the MARA, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural UniversityDepartment of Developmental Biology, State Key Laboratory of Organ Failure Research, School of Basic Medical Sciences, Southern Medical UniversityCancer Center, Faculty of Health Sciences, University of MacauCancer Center, Faculty of Health Sciences, University of MacauAbstract Cancer metastasis is the primary cause of cancer-related death, yet the forces that drive cancer cells through various steps and different routes to distinct target organs/tissues remain elusive. In this study, we applied a barcoding system based single-cell lineage tracing approach to study the metastasis rate and route of breast cancer cells and their interactions with the tumor microenvironment (TME) during metastasis. The results indicate that only a small fraction of cells, accounting for fewer than 3% of total barcodes, can intravasate from the primary site into the blood circulation, whereas more cells disseminate through the lymphatic system to different organs. Tumor cells derived from the same progenitor cell exhibit different gene expression patterns in different soils, and the cancer cell-TME communication paradigm varies significantly between primary and metastatic tumors. Furthermore, metastable cells require a prewired particular cytokine expression ability which may be specific for lymph metastasis route although the underlying mechanism requires further investigation. In summary, leveraging a single-cell lineage tracing system, we demonstrate that the crosstalk between tumor cells and the TME is the driving force controlling the preferential metastatic fate of cancer cells through the lymphatic system. Graphical Abstracthttps://doi.org/10.1186/s12943-025-02279-wBarcode systemLymphatic metastasisLineage tracingTumor microenvironmentSoil-seed interaction |
| spellingShingle | Kai Miao Aiping Zhang Xiaodan Yang Yipeng Zhang Anqi Lin Lijian Wang Xin Zhang Heng Sun Jun Xu Jingyao Zhang Yuzhao Feng Fangyuan Shao Sen Guo Zhihui Weng Peng Luo Dong Wang Shuai Gao Xiao-Yang Zhao Xiaoling Xu Chu-Xia Deng Lymphatic system is the mainstream for breast cancer dissemination and metastasis revealed by single-cell lineage tracing Molecular Cancer Barcode system Lymphatic metastasis Lineage tracing Tumor microenvironment Soil-seed interaction |
| title | Lymphatic system is the mainstream for breast cancer dissemination and metastasis revealed by single-cell lineage tracing |
| title_full | Lymphatic system is the mainstream for breast cancer dissemination and metastasis revealed by single-cell lineage tracing |
| title_fullStr | Lymphatic system is the mainstream for breast cancer dissemination and metastasis revealed by single-cell lineage tracing |
| title_full_unstemmed | Lymphatic system is the mainstream for breast cancer dissemination and metastasis revealed by single-cell lineage tracing |
| title_short | Lymphatic system is the mainstream for breast cancer dissemination and metastasis revealed by single-cell lineage tracing |
| title_sort | lymphatic system is the mainstream for breast cancer dissemination and metastasis revealed by single cell lineage tracing |
| topic | Barcode system Lymphatic metastasis Lineage tracing Tumor microenvironment Soil-seed interaction |
| url | https://doi.org/10.1186/s12943-025-02279-w |
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