Tissue-resident glial cells associate with tumoral vasculature and promote cancer progression

IF 9.2 1区 医学 Q1 PERIPHERAL VASCULAR DISEASE Angiogenesis Pub Date : 2022-10-01 DOI:10.1007/s10456-022-09858-1
Beatriz G. S. Rocha, Caroline C. Picoli, Bryan O. P. Gonçalves, Walison N. Silva, Alinne C. Costa, Michele M. Moraes, Pedro A. C. Costa, Gabryella S. P. Santos, Milla R. Almeida, Luciana M. Silva, Youvika Singh, Marcelo Falchetti, Gabriela D. A. Guardia, Pedro P. G. Guimarães, Remo C. Russo, Rodrigo R. Resende, Mauro C. X. Pinto, Jaime H. Amorim, Vasco A. C. Azevedo, Alexandre Kanashiro, Helder I. Nakaya, Edroaldo L. Rocha, Pedro A. F. Galante, Akiva Mintz, Paul S. Frenette, Alexander Birbrair
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引用次数: 2

Abstract

Cancer cells are embedded within the tissue and interact dynamically with its components during cancer progression. Understanding the contribution of cellular components within the tumor microenvironment is crucial for the success of therapeutic applications. Here, we reveal the presence of perivascular GFAP+/Plp1+ cells within the tumor microenvironment. Using in vivo inducible Cre/loxP mediated systems, we demonstrated that these cells derive from tissue-resident Schwann cells. Genetic ablation of endogenous Schwann cells slowed down tumor growth and angiogenesis. Schwann cell-specific depletion also induced a boost in the immune surveillance by increasing tumor-infiltrating anti-tumor lymphocytes, while reducing immune-suppressor cells. In humans, a retrospective in silico analysis of tumor biopsies revealed that increased expression of Schwann cell-related genes within melanoma was associated with improved survival. Collectively, our study suggests that Schwann cells regulate tumor progression, indicating that manipulation of Schwann cells may provide a valuable tool to improve cancer patients’ outcomes.

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组织侧胶质细胞与肿瘤血管系统相关并促进癌症进展
癌症细胞嵌入组织中,并在癌症进展过程中与其成分动态相互作用。了解肿瘤微环境中细胞成分的贡献对于治疗应用的成功至关重要。在这里,我们揭示了肿瘤微环境中血管周围GFAP+/Plp1+细胞的存在。使用体内诱导型Cre/loxP介导的系统,我们证明这些细胞来源于组织固有的施旺细胞。内源性施旺细胞的基因消融减缓了肿瘤生长和血管生成。雪旺细胞特异性耗竭还通过增加肿瘤浸润的抗肿瘤淋巴细胞,同时减少免疫抑制细胞,诱导免疫监测的增强。在人类中,一项对肿瘤活检的回顾性计算机分析显示,黑色素瘤中施旺细胞相关基因表达的增加与生存率的提高有关。总之,我们的研究表明,施旺细胞调节肿瘤进展,这表明施旺细胞的操作可能为改善癌症患者的预后提供有价值的工具。
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来源期刊
Angiogenesis
Angiogenesis PERIPHERAL VASCULAR DISEASE-
CiteScore
21.90
自引率
8.20%
发文量
37
审稿时长
6-12 weeks
期刊介绍: Angiogenesis, a renowned international journal, seeks to publish high-quality original articles and reviews on the cellular and molecular mechanisms governing angiogenesis in both normal and pathological conditions. By serving as a primary platform for swift communication within the field of angiogenesis research, this multidisciplinary journal showcases pioneering experimental studies utilizing molecular techniques, in vitro methods, animal models, and clinical investigations into angiogenic diseases. Furthermore, Angiogenesis sheds light on cutting-edge therapeutic strategies for promoting or inhibiting angiogenesis, while also highlighting fresh markers and techniques for disease diagnosis and prognosis.
期刊最新文献
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