{"title":"TNFSF15促进肿瘤中CD11b+髓系细胞分化为血管周细胞。","authors":"Xiangxiang Gu, Yipan Zhu, Cancan Zhao, Yixin Cao, Jingying Wang, Qiangzhe Zhang, Luyuan Li","doi":"10.20892/j.issn.2095-3941.2023.0245","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>Immature vasculature lacking pericyte coverage substantially contributes to tumor growth, drug resistance, and cancer cell dissemination. We previously demonstrated that tumor necrosis factor superfamily 15 (TNFSF15) is a cytokine with important roles in modulating hematopoiesis and vascular homeostasis. The main purpose of this study was to explore whether TNFSF15 might promote freshly isolated myeloid cells to differentiate into CD11b<sup>+</sup> cells and further into pericytes.</p><p><strong>Methods: </strong>A model of Lewis lung cancer was established in mice with red fluorescent bone marrow. After TNFSF15 treatment, CD11b<sup>+</sup> myeloid cells and vascular pericytes in the tumors, and the co-localization of pericytes and vascular endothelial cells, were assessed. Additionally, CD11b<sup>+</sup> cells were isolated from wild-type mice and treated with TNFSF15 to determine the effects on the differentiation of these cells.</p><p><strong>Results: </strong>We observed elevated percentages of bone marrow-derived CD11b<sup>+</sup> myeloid cells and vascular pericytes in TNFSF15-treated tumors, and the latter cells co-localized with vascular endothelial cells. TNFSF15 protected against CD11b<sup>+</sup> cell apoptosis and facilitated the differentiation of these cells into pericytes by down-regulating Wnt3a-VEGFR1 and up-regulating CD49e-FN signaling pathways.</p><p><strong>Conclusions: </strong>TNFSF15 facilitates the production of CD11b<sup>+</sup> cells in the bone marrow and promotes the differentiation of these cells into pericytes, which may stabilize the tumor neovasculature.</p>","PeriodicalId":9611,"journal":{"name":"Cancer Biology & Medicine","volume":null,"pages":null},"PeriodicalIF":5.6000,"publicationDate":"2023-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10690882/pdf/","citationCount":"0","resultStr":"{\"title\":\"TNFSF15 facilitates the differentiation of CD11b<sup>+</sup> myeloid cells into vascular pericytes in tumors.\",\"authors\":\"Xiangxiang Gu, Yipan Zhu, Cancan Zhao, Yixin Cao, Jingying Wang, Qiangzhe Zhang, Luyuan Li\",\"doi\":\"10.20892/j.issn.2095-3941.2023.0245\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>Immature vasculature lacking pericyte coverage substantially contributes to tumor growth, drug resistance, and cancer cell dissemination. We previously demonstrated that tumor necrosis factor superfamily 15 (TNFSF15) is a cytokine with important roles in modulating hematopoiesis and vascular homeostasis. The main purpose of this study was to explore whether TNFSF15 might promote freshly isolated myeloid cells to differentiate into CD11b<sup>+</sup> cells and further into pericytes.</p><p><strong>Methods: </strong>A model of Lewis lung cancer was established in mice with red fluorescent bone marrow. After TNFSF15 treatment, CD11b<sup>+</sup> myeloid cells and vascular pericytes in the tumors, and the co-localization of pericytes and vascular endothelial cells, were assessed. Additionally, CD11b<sup>+</sup> cells were isolated from wild-type mice and treated with TNFSF15 to determine the effects on the differentiation of these cells.</p><p><strong>Results: </strong>We observed elevated percentages of bone marrow-derived CD11b<sup>+</sup> myeloid cells and vascular pericytes in TNFSF15-treated tumors, and the latter cells co-localized with vascular endothelial cells. TNFSF15 protected against CD11b<sup>+</sup> cell apoptosis and facilitated the differentiation of these cells into pericytes by down-regulating Wnt3a-VEGFR1 and up-regulating CD49e-FN signaling pathways.</p><p><strong>Conclusions: </strong>TNFSF15 facilitates the production of CD11b<sup>+</sup> cells in the bone marrow and promotes the differentiation of these cells into pericytes, which may stabilize the tumor neovasculature.</p>\",\"PeriodicalId\":9611,\"journal\":{\"name\":\"Cancer Biology & Medicine\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":5.6000,\"publicationDate\":\"2023-11-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10690882/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cancer Biology & Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.20892/j.issn.2095-3941.2023.0245\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Biology & Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.20892/j.issn.2095-3941.2023.0245","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
TNFSF15 facilitates the differentiation of CD11b+ myeloid cells into vascular pericytes in tumors.
Objective: Immature vasculature lacking pericyte coverage substantially contributes to tumor growth, drug resistance, and cancer cell dissemination. We previously demonstrated that tumor necrosis factor superfamily 15 (TNFSF15) is a cytokine with important roles in modulating hematopoiesis and vascular homeostasis. The main purpose of this study was to explore whether TNFSF15 might promote freshly isolated myeloid cells to differentiate into CD11b+ cells and further into pericytes.
Methods: A model of Lewis lung cancer was established in mice with red fluorescent bone marrow. After TNFSF15 treatment, CD11b+ myeloid cells and vascular pericytes in the tumors, and the co-localization of pericytes and vascular endothelial cells, were assessed. Additionally, CD11b+ cells were isolated from wild-type mice and treated with TNFSF15 to determine the effects on the differentiation of these cells.
Results: We observed elevated percentages of bone marrow-derived CD11b+ myeloid cells and vascular pericytes in TNFSF15-treated tumors, and the latter cells co-localized with vascular endothelial cells. TNFSF15 protected against CD11b+ cell apoptosis and facilitated the differentiation of these cells into pericytes by down-regulating Wnt3a-VEGFR1 and up-regulating CD49e-FN signaling pathways.
Conclusions: TNFSF15 facilitates the production of CD11b+ cells in the bone marrow and promotes the differentiation of these cells into pericytes, which may stabilize the tumor neovasculature.
期刊介绍:
Cancer Biology & Medicine (ISSN 2095-3941) is a peer-reviewed open-access journal of Chinese Anti-cancer Association (CACA), which is the leading professional society of oncology in China. The journal quarterly provides innovative and significant information on biological basis of cancer, cancer microenvironment, translational cancer research, and all aspects of clinical cancer research. The journal also publishes significant perspectives on indigenous cancer types in China.