干细胞
CXCR4型
脑膜瘤
癌症研究
脑膜
生物
癌症干细胞
病理
恶性脑膜瘤
趋化因子受体
CXCL14型
趋化因子
免疫学
医学
细胞生物学
炎症
作者
Federica Barbieri,Adriana Bajetto,Irene Dellacasagrande,Agnese Solari,Roberto Würth,Virgínia Fernández,Silvia Rancati,Davide Ceresa,Irene Appolloni,Giuseppa De Luca,Mariella Dono,Paolo Nozza,P. Schiapparelli,M. Gambaro,Pietro Fiaschi,Gabriele Gaggero,Niccolò Costanzo,Stefano Thellung,Paolo Malatesta,Aldo Pagano,Gianluigi Zona,Davide De Pietri Tonelli,Tullio Florio
出处
期刊:Neuro-oncology
[Oxford University Press]
日期:2023-04-19
卷期号:25 (10): 1775-1787
标识
DOI:10.1093/neuonc/noad076
摘要
Meningiomas are mainly benign brain tumors, although about 20% of histologically benign cases are clinically aggressive and recur after resection. We hypothesize that meningioma brain invasiveness and recurrence may be related to the presence of cancer stem cells and their high responsiveness to the CXCL12-CXCR4/CXCR7 chemokine axis. The aim of this study was to isolate meningioma stem cells from human samples, characterize them for biological features related to malignant behavior, and to identify the role of CXCR4/CXCR7 in these processes.Meningioma stem cells were isolated from patient-derived primary cultures in stem cell-permissive conditions, and characterized for phenotype, self-renewal, proliferation and migration rates, vasculogenic mimicry (VM), and in vivo tumorigenesis, in comparison with differentiated meningioma cells and stem-like cells isolated from normal meninges. These cell populations were challenged with CXCL12 and CXCL11 and receptor antagonists to define the chemokine role in stem cell-related functions.Stem-like cells isolated from meningioma cultures display higher proliferation and migration rates, and VM, as compared to meningioma non-stem cells or cells isolated from normal meninges and were the only tumorigenic population in vivo. In meningioma cells, these stem-like functions were under the control of the CXCR4/CXCR7 chemokine axis.We report a role for CXCL11 and CXCL12 in the control of malignant features in stem-like cells isolated from human meningioma, providing a possible basis for the aggressive clinical behavior observed in subsets of these tumors. CXCR4/CXCR7 antagonists might represent a useful approach for meningioma at high risk of recurrence and malignant progression.
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