Exosomal PVRL4 Promotes Lung Adenocarcinoma Progression by Enhancing the Generation of Myeloid‐Derived Suppressor Cell‐Secreted TGF‐β1
ABSTRACT Background The cancer cell marker poliovirus receptor‐like protein 4 (PVRL4) has been shown to be highly expressed in many cancers, including lung cancer. Myeloid‐derived suppressor cells (MDSCs) are a population of immature myeloid cells with immunosuppressive roles that can attenuate the...
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| Format: | Article |
| Language: | English |
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Wiley
2025-01-01
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| Series: | Thoracic Cancer |
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| Online Access: | https://doi.org/10.1111/1759-7714.15495 |
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| author | Yahai Liang Jinmei Li Lihua Zhang Jinling Zhou Meilian Liu Xiaoxia Peng Weizhen Zheng Zhennan Lai |
| author_facet | Yahai Liang Jinmei Li Lihua Zhang Jinling Zhou Meilian Liu Xiaoxia Peng Weizhen Zheng Zhennan Lai |
| author_sort | Yahai Liang |
| collection | DOAJ |
| description | ABSTRACT Background The cancer cell marker poliovirus receptor‐like protein 4 (PVRL4) has been shown to be highly expressed in many cancers, including lung cancer. Myeloid‐derived suppressor cells (MDSCs) are a population of immature myeloid cells with immunosuppressive roles that can attenuate the anticancer response. Here, the precise functions and the relationship between PVRL4 and MDSCs in lung adenocarcinoma (LUAD) progression were investigated. Methods Detection of levels of mRNAs and proteins was conducted using qRT‐PCR and western blotting. The CCK‐8, colony formation, transwell, wound healing assays, and flow cytometry were used to explore cell growth, invasion, migration, and apoptosis, respectively. ELISA analysis detected TGF‐β1 contents. LUAD mouse models were established for in vivo assay. Exosomes were isolated by ultracentrifugation. MDSCs were induced from peripheral blood mononuclear cells (PBMCs) by cytokine or co‐culture with cancer cells. Results LUAD tissues and cells showed high PVRL4 expression, and PVRL4 deficiency suppressed LUAD cell proliferation, invasion, migration, and induced cell apoptosis in vitro, and impeded LUAD growth in vivo. Thereafter, we found that PVRL4 was packaged into exosomes in LUAD cells, and could be transferred into PBMCs to promote MDSC induction and the expression of MDSC‐secreted TGF‐β1. Functionally, the silencing of exosomal PVRL4 impaired LUAD cell proliferation, invasion, migration, and evoked cell apoptosis, which could be reversed by the incubation of TGF‐β1‐overexpressed MDSCs. Conclusion Exosomal PVRL4 promoted LUAD progression by inducing the secretion of TGF‐β1 in MDSCs, indicating a novel direction for LUAD immunotherapy. |
| format | Article |
| id | doaj-art-ad1886af82394c96b20278cc242b2a5a |
| institution | Kabale University |
| issn | 1759-7706 1759-7714 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Thoracic Cancer |
| spelling | doaj-art-ad1886af82394c96b20278cc242b2a5a2025-01-30T22:40:34ZengWileyThoracic Cancer1759-77061759-77142025-01-01162n/an/a10.1111/1759-7714.15495Exosomal PVRL4 Promotes Lung Adenocarcinoma Progression by Enhancing the Generation of Myeloid‐Derived Suppressor Cell‐Secreted TGF‐β1Yahai Liang0Jinmei Li1Lihua Zhang2Jinling Zhou3Meilian Liu4Xiaoxia Peng5Weizhen Zheng6Zhennan Lai7Department of Pulmonary Oncology Affiliated Hospital of Guangdong Medical University Zhanjiang ChinaDepartment of Pulmonary Oncology Affiliated Hospital of Guangdong Medical University Zhanjiang ChinaDepartment of Pulmonary Oncology Affiliated Hospital of Guangdong Medical University Zhanjiang ChinaAnesthesia Surgery Center Affiliated Hospital of Guangdong Medical University Zhanjiang ChinaDepartment of Pulmonary Oncology Affiliated Hospital of Guangdong Medical University Zhanjiang ChinaDepartment of Pulmonary Oncology Affiliated Hospital of Guangdong Medical University Zhanjiang ChinaDepartment of Pulmonary Oncology Affiliated Hospital of Guangdong Medical University Zhanjiang ChinaDepartment of Pulmonary Oncology Affiliated Hospital of Guangdong Medical University Zhanjiang ChinaABSTRACT Background The cancer cell marker poliovirus receptor‐like protein 4 (PVRL4) has been shown to be highly expressed in many cancers, including lung cancer. Myeloid‐derived suppressor cells (MDSCs) are a population of immature myeloid cells with immunosuppressive roles that can attenuate the anticancer response. Here, the precise functions and the relationship between PVRL4 and MDSCs in lung adenocarcinoma (LUAD) progression were investigated. Methods Detection of levels of mRNAs and proteins was conducted using qRT‐PCR and western blotting. The CCK‐8, colony formation, transwell, wound healing assays, and flow cytometry were used to explore cell growth, invasion, migration, and apoptosis, respectively. ELISA analysis detected TGF‐β1 contents. LUAD mouse models were established for in vivo assay. Exosomes were isolated by ultracentrifugation. MDSCs were induced from peripheral blood mononuclear cells (PBMCs) by cytokine or co‐culture with cancer cells. Results LUAD tissues and cells showed high PVRL4 expression, and PVRL4 deficiency suppressed LUAD cell proliferation, invasion, migration, and induced cell apoptosis in vitro, and impeded LUAD growth in vivo. Thereafter, we found that PVRL4 was packaged into exosomes in LUAD cells, and could be transferred into PBMCs to promote MDSC induction and the expression of MDSC‐secreted TGF‐β1. Functionally, the silencing of exosomal PVRL4 impaired LUAD cell proliferation, invasion, migration, and evoked cell apoptosis, which could be reversed by the incubation of TGF‐β1‐overexpressed MDSCs. Conclusion Exosomal PVRL4 promoted LUAD progression by inducing the secretion of TGF‐β1 in MDSCs, indicating a novel direction for LUAD immunotherapy.https://doi.org/10.1111/1759-7714.15495exosomeimmunosuppressive activityLUADMDSCsPBMCsPVRL4 |
| spellingShingle | Yahai Liang Jinmei Li Lihua Zhang Jinling Zhou Meilian Liu Xiaoxia Peng Weizhen Zheng Zhennan Lai Exosomal PVRL4 Promotes Lung Adenocarcinoma Progression by Enhancing the Generation of Myeloid‐Derived Suppressor Cell‐Secreted TGF‐β1 Thoracic Cancer exosome immunosuppressive activity LUAD MDSCs PBMCs PVRL4 |
| title | Exosomal PVRL4 Promotes Lung Adenocarcinoma Progression by Enhancing the Generation of Myeloid‐Derived Suppressor Cell‐Secreted TGF‐β1 |
| title_full | Exosomal PVRL4 Promotes Lung Adenocarcinoma Progression by Enhancing the Generation of Myeloid‐Derived Suppressor Cell‐Secreted TGF‐β1 |
| title_fullStr | Exosomal PVRL4 Promotes Lung Adenocarcinoma Progression by Enhancing the Generation of Myeloid‐Derived Suppressor Cell‐Secreted TGF‐β1 |
| title_full_unstemmed | Exosomal PVRL4 Promotes Lung Adenocarcinoma Progression by Enhancing the Generation of Myeloid‐Derived Suppressor Cell‐Secreted TGF‐β1 |
| title_short | Exosomal PVRL4 Promotes Lung Adenocarcinoma Progression by Enhancing the Generation of Myeloid‐Derived Suppressor Cell‐Secreted TGF‐β1 |
| title_sort | exosomal pvrl4 promotes lung adenocarcinoma progression by enhancing the generation of myeloid derived suppressor cell secreted tgf β1 |
| topic | exosome immunosuppressive activity LUAD MDSCs PBMCs PVRL4 |
| url | https://doi.org/10.1111/1759-7714.15495 |
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