Cancer stem cells promote lymph nodes metastasis of breast cancer by reprogramming tumor microenvironment
Breast cancer progression and metastasis are governed by a complex interplay within the tumor immune microenvironment (TIME), involving numerous cell types. Lymph node metastasis (LNM) is a key prognostic marker associated with distant organ metastasis and reduced patient survival, but the mechanism...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-09-01
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| Series: | Translational Oncology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523323001195 |
| _version_ | 1797778372721377280 |
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| author | Lin Li Jianyu Liu Wenzheng Wang Yingqiang Fu Yuhan Deng Xin Li Zhuolin Liu Yuheng Pang Yangyang Xu Meisi Yan Zhigao Li |
| author_facet | Lin Li Jianyu Liu Wenzheng Wang Yingqiang Fu Yuhan Deng Xin Li Zhuolin Liu Yuheng Pang Yangyang Xu Meisi Yan Zhigao Li |
| author_sort | Lin Li |
| collection | DOAJ |
| description | Breast cancer progression and metastasis are governed by a complex interplay within the tumor immune microenvironment (TIME), involving numerous cell types. Lymph node metastasis (LNM) is a key prognostic marker associated with distant organ metastasis and reduced patient survival, but the mechanisms underlying its promotion by breast cancer stem cells (CSCs) remain unclear. Our study sought to unravel how CSCs reprogram TIME to facilitate LNM. Utilizing single-cell RNA sequencing, we profiled TIME in primary cancer and corresponding metastatic lymph node samples from patients at our institution. To verify the derived data, we cultured CSCs and performed validation assays employing flow cytometry and CyTOF. Our analysis revealed distinct differences in cellular infiltration patterns between tumor and LNM samples. Importantly, RAC2 and PTTG1 double-positive CSCs, which exhibit the highest stem-like attributes, were markedly enriched in metastatic lymph nodes. These CSCs are hypothesized to foster metastasis via activation of specific metastasis-related transcription factors and signaling pathways. Additionally, our data suggest that CSCs might modulate adaptive and innate immune cell evolution, thereby further contributing to metastasis. In summary, this study illuminates a critical role of CSCs in modifying TIME to facilitate LNM. The enrichment of highly stem-like CSCs in metastatic lymph nodes offers novel therapeutic targeting opportunities and deepens our understanding of breast cancer metastasis. |
| first_indexed | 2024-03-12T23:17:22Z |
| format | Article |
| id | doaj.art-639f106f5758448a9f57e09313f6abdf |
| institution | Directory Open Access Journal |
| issn | 1936-5233 |
| language | English |
| last_indexed | 2024-03-12T23:17:22Z |
| publishDate | 2023-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj.art-639f106f5758448a9f57e09313f6abdf2023-07-17T04:07:36ZengElsevierTranslational Oncology1936-52332023-09-0135101733Cancer stem cells promote lymph nodes metastasis of breast cancer by reprogramming tumor microenvironmentLin Li0Jianyu Liu1Wenzheng Wang2Yingqiang Fu3Yuhan Deng4Xin Li5Zhuolin Liu6Yuheng Pang7Yangyang Xu8Meisi Yan9Zhigao Li10Harbin Medical University Cancer Hospital, Harbin Medical University, No.150 Haping Rd, Nangang District, Harbin 150081, ChinaHarbin Medical University Cancer Hospital, Harbin Medical University, No.150 Haping Rd, Nangang District, Harbin 150081, ChinaHarbin Medical University Cancer Hospital, Harbin Medical University, No.150 Haping Rd, Nangang District, Harbin 150081, ChinaHarbin Medical University Cancer Hospital, Harbin Medical University, No.150 Haping Rd, Nangang District, Harbin 150081, ChinaHarbin Medical University Cancer Hospital, Harbin Medical University, No.150 Haping Rd, Nangang District, Harbin 150081, ChinaHarbin Medical University Cancer Hospital, Harbin Medical University, No.150 Haping Rd, Nangang District, Harbin 150081, ChinaHarbin Medical University Cancer Hospital, Harbin Medical University, No.150 Haping Rd, Nangang District, Harbin 150081, ChinaHarbin Medical University Cancer Hospital, Harbin Medical University, No.150 Haping Rd, Nangang District, Harbin 150081, ChinaHarbin Medical University Cancer Hospital, Harbin Medical University, No.150 Haping Rd, Nangang District, Harbin 150081, ChinaDepartment of Pathology, Harbin Medical University, Harbin, ChinaHarbin Medical University Cancer Hospital, Harbin Medical University, No.150 Haping Rd, Nangang District, Harbin 150081, China; Corresponding author.Breast cancer progression and metastasis are governed by a complex interplay within the tumor immune microenvironment (TIME), involving numerous cell types. Lymph node metastasis (LNM) is a key prognostic marker associated with distant organ metastasis and reduced patient survival, but the mechanisms underlying its promotion by breast cancer stem cells (CSCs) remain unclear. Our study sought to unravel how CSCs reprogram TIME to facilitate LNM. Utilizing single-cell RNA sequencing, we profiled TIME in primary cancer and corresponding metastatic lymph node samples from patients at our institution. To verify the derived data, we cultured CSCs and performed validation assays employing flow cytometry and CyTOF. Our analysis revealed distinct differences in cellular infiltration patterns between tumor and LNM samples. Importantly, RAC2 and PTTG1 double-positive CSCs, which exhibit the highest stem-like attributes, were markedly enriched in metastatic lymph nodes. These CSCs are hypothesized to foster metastasis via activation of specific metastasis-related transcription factors and signaling pathways. Additionally, our data suggest that CSCs might modulate adaptive and innate immune cell evolution, thereby further contributing to metastasis. In summary, this study illuminates a critical role of CSCs in modifying TIME to facilitate LNM. The enrichment of highly stem-like CSCs in metastatic lymph nodes offers novel therapeutic targeting opportunities and deepens our understanding of breast cancer metastasis.http://www.sciencedirect.com/science/article/pii/S1936523323001195Breast cancer 1Cancer stem cells (CSCs) 2Tumor immune microenvironment (TIME) 3Single-cell RNA sequencing (scRNA-seq) 4Lymph node metastasis 5 |
| spellingShingle | Lin Li Jianyu Liu Wenzheng Wang Yingqiang Fu Yuhan Deng Xin Li Zhuolin Liu Yuheng Pang Yangyang Xu Meisi Yan Zhigao Li Cancer stem cells promote lymph nodes metastasis of breast cancer by reprogramming tumor microenvironment Translational Oncology Breast cancer 1 Cancer stem cells (CSCs) 2 Tumor immune microenvironment (TIME) 3 Single-cell RNA sequencing (scRNA-seq) 4 Lymph node metastasis 5 |
| title | Cancer stem cells promote lymph nodes metastasis of breast cancer by reprogramming tumor microenvironment |
| title_full | Cancer stem cells promote lymph nodes metastasis of breast cancer by reprogramming tumor microenvironment |
| title_fullStr | Cancer stem cells promote lymph nodes metastasis of breast cancer by reprogramming tumor microenvironment |
| title_full_unstemmed | Cancer stem cells promote lymph nodes metastasis of breast cancer by reprogramming tumor microenvironment |
| title_short | Cancer stem cells promote lymph nodes metastasis of breast cancer by reprogramming tumor microenvironment |
| title_sort | cancer stem cells promote lymph nodes metastasis of breast cancer by reprogramming tumor microenvironment |
| topic | Breast cancer 1 Cancer stem cells (CSCs) 2 Tumor immune microenvironment (TIME) 3 Single-cell RNA sequencing (scRNA-seq) 4 Lymph node metastasis 5 |
| url | http://www.sciencedirect.com/science/article/pii/S1936523323001195 |
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