SPP1+ TAM Regulates the Metastatic Colonization of CXCR4+ Metastasis‐Associated Tumor Cells by Remodeling the Lymph Node Microenvironment
Abstract Lymph node metastasis, the initial step in distant metastasis, represents a primary contributor to mortality in patients diagnosed with oral squamous cell carcinoma (OSCC). However, the underlying mechanisms of lymph node metastasis in OSCC remain incompletely understood. Here, the transcri...
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| Format: | Article |
| Language: | English |
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Wiley
2024-11-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202400524 |
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| author | Liang Dong Shujun Hu Xin Li Shiyao Pei Liping Jin Lining Zhang Xiang Chen Anjie Min Mingzhu Yin |
| author_facet | Liang Dong Shujun Hu Xin Li Shiyao Pei Liping Jin Lining Zhang Xiang Chen Anjie Min Mingzhu Yin |
| author_sort | Liang Dong |
| collection | DOAJ |
| description | Abstract Lymph node metastasis, the initial step in distant metastasis, represents a primary contributor to mortality in patients diagnosed with oral squamous cell carcinoma (OSCC). However, the underlying mechanisms of lymph node metastasis in OSCC remain incompletely understood. Here, the transcriptomes of 56 383 single cells derived from paired tissues of six OSCC patients are analyzed. This study founds that CXCR4+ epithelial cells, identified as highly malignant disseminated tumor cells (DTCs), exhibited a propensity for lymph node metastasis. Importantly, a distinct subset of tumor‐associated macrophages (TAMs) characterized by exclusive expression of phosphoprotein 1 (SPP1) is discovered. These TAMs may remodel the metastatic lymph node microenvironment by potentially activating fibroblasts and promoting T cell exhaustion through SPP1‐CD44 and CD155‐CD226 ligand‐receptor interactions, thereby facilitating colonization and proliferation of disseminated tumor cells. The research advanced the mechanistic understanding of metastatic tumor microenvironment (TME) and provided a foundation for the development of personalized treatments for OSCC patients with metastasis. |
| format | Article |
| id | doaj-art-8ba185cdca0b46438d63dbaa5b98ae70 |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-8ba185cdca0b46438d63dbaa5b98ae702024-11-27T11:21:53ZengWileyAdvanced Science2198-38442024-11-011144n/an/a10.1002/advs.202400524SPP1+ TAM Regulates the Metastatic Colonization of CXCR4+ Metastasis‐Associated Tumor Cells by Remodeling the Lymph Node MicroenvironmentLiang Dong0Shujun Hu1Xin Li2Shiyao Pei3Liping Jin4Lining Zhang5Xiang Chen6Anjie Min7Mingzhu Yin8Department of Dermatology Hunan Engineering Research Center of Skin Health and Disease Hunan Key Laboratory of Skin Cancer and Psoriasis Xiangya Hospital Central South University Changsha Hunan 410008 ChinaNational Clinical Research Center for Geriatric Disorders Xiangya Hospital Central South University Changsha Hunan 410008 ChinaClinical Research Center (CRC) Medical Pathology Center (MPC) Cancer Early Detection and Treatment Center (CEDTC) Chongqing University Three Gorges Hospital Chongqing University Chongqing 404100 ChinaDepartment of Dermatology Hunan Engineering Research Center of Skin Health and Disease Hunan Key Laboratory of Skin Cancer and Psoriasis Xiangya Hospital Central South University Changsha Hunan 410008 ChinaDepartment of Dermatology Hunan Engineering Research Center of Skin Health and Disease Hunan Key Laboratory of Skin Cancer and Psoriasis Xiangya Hospital Central South University Changsha Hunan 410008 ChinaClinical Research Center (CRC) Medical Pathology Center (MPC) Cancer Early Detection and Treatment Center (CEDTC) Chongqing University Three Gorges Hospital Chongqing University Chongqing 404100 ChinaDepartment of Dermatology Hunan Engineering Research Center of Skin Health and Disease Hunan Key Laboratory of Skin Cancer and Psoriasis Xiangya Hospital Central South University Changsha Hunan 410008 ChinaNational Clinical Research Center for Geriatric Disorders Xiangya Hospital Central South University Changsha Hunan 410008 ChinaDepartment of Dermatology Hunan Engineering Research Center of Skin Health and Disease Hunan Key Laboratory of Skin Cancer and Psoriasis Xiangya Hospital Central South University Changsha Hunan 410008 ChinaAbstract Lymph node metastasis, the initial step in distant metastasis, represents a primary contributor to mortality in patients diagnosed with oral squamous cell carcinoma (OSCC). However, the underlying mechanisms of lymph node metastasis in OSCC remain incompletely understood. Here, the transcriptomes of 56 383 single cells derived from paired tissues of six OSCC patients are analyzed. This study founds that CXCR4+ epithelial cells, identified as highly malignant disseminated tumor cells (DTCs), exhibited a propensity for lymph node metastasis. Importantly, a distinct subset of tumor‐associated macrophages (TAMs) characterized by exclusive expression of phosphoprotein 1 (SPP1) is discovered. These TAMs may remodel the metastatic lymph node microenvironment by potentially activating fibroblasts and promoting T cell exhaustion through SPP1‐CD44 and CD155‐CD226 ligand‐receptor interactions, thereby facilitating colonization and proliferation of disseminated tumor cells. The research advanced the mechanistic understanding of metastatic tumor microenvironment (TME) and provided a foundation for the development of personalized treatments for OSCC patients with metastasis.https://doi.org/10.1002/advs.202400524lymph node metastatic microenvironmentmacrophageoral squamous cell carcinomasingle cell RNA sequencingSPP1 |
| spellingShingle | Liang Dong Shujun Hu Xin Li Shiyao Pei Liping Jin Lining Zhang Xiang Chen Anjie Min Mingzhu Yin SPP1+ TAM Regulates the Metastatic Colonization of CXCR4+ Metastasis‐Associated Tumor Cells by Remodeling the Lymph Node Microenvironment Advanced Science lymph node metastatic microenvironment macrophage oral squamous cell carcinoma single cell RNA sequencing SPP1 |
| title | SPP1+ TAM Regulates the Metastatic Colonization of CXCR4+ Metastasis‐Associated Tumor Cells by Remodeling the Lymph Node Microenvironment |
| title_full | SPP1+ TAM Regulates the Metastatic Colonization of CXCR4+ Metastasis‐Associated Tumor Cells by Remodeling the Lymph Node Microenvironment |
| title_fullStr | SPP1+ TAM Regulates the Metastatic Colonization of CXCR4+ Metastasis‐Associated Tumor Cells by Remodeling the Lymph Node Microenvironment |
| title_full_unstemmed | SPP1+ TAM Regulates the Metastatic Colonization of CXCR4+ Metastasis‐Associated Tumor Cells by Remodeling the Lymph Node Microenvironment |
| title_short | SPP1+ TAM Regulates the Metastatic Colonization of CXCR4+ Metastasis‐Associated Tumor Cells by Remodeling the Lymph Node Microenvironment |
| title_sort | spp1 tam regulates the metastatic colonization of cxcr4 metastasis associated tumor cells by remodeling the lymph node microenvironment |
| topic | lymph node metastatic microenvironment macrophage oral squamous cell carcinoma single cell RNA sequencing SPP1 |
| url | https://doi.org/10.1002/advs.202400524 |
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