脑肿瘤干细胞的血管周围微环境

A perivascular niche for brain tumor stem cells.

作者信息

Calabrese Christopher, Poppleton Helen, Kocak Mehmet, Hogg Twala L, Fuller Christine, Hamner Blair, Oh Eun Young, Gaber M Waleed, Finklestein David, Allen Meredith, Frank Adrian, Bayazitov Ildar T, Zakharenko Stanislav S, Gajjar Amar, Davidoff Andrew, Gilbertson Richard J

机构信息

Department of Developmental Neurobiology, St. Jude Children's Research Hospital, 332 North Lauderdale Street, Memphis, TN 38105, USA.

出版信息

Cancer Cell. 2007 Jan;11(1):69-82. doi: 10.1016/j.ccr.2006.11.020.

DOI:10.1016/j.ccr.2006.11.020

PMID:17222791

Abstract

Cancers are believed to arise from cancer stem cells (CSCs), but it is not known if these cells remain dependent upon the niche microenvironments that regulate normal stem cells. We show that endothelial cells interact closely with self-renewing brain tumor cells and secrete factors that maintain these cells in a stem cell-like state. Increasing the number of endothelial cells or blood vessels in orthotopic brain tumor xenografts expanded the fraction of self-renewing cells and accelerated the initiation and growth of tumors. Conversely, depletion of blood vessels from xenografts ablated self-renewing cells from tumors and arrested tumor growth. We propose that brain CSCs are maintained within vascular niches that are important targets for therapeutic approaches.

摘要

癌症被认为起源于癌症干细胞（CSCs），但目前尚不清楚这些细胞是否仍然依赖于调节正常干细胞的生态位微环境。我们发现内皮细胞与自我更新的脑肿瘤细胞密切相互作用，并分泌维持这些细胞处于干细胞样状态的因子。增加原位脑肿瘤异种移植中内皮细胞或血管的数量，可扩大自我更新细胞的比例，并加速肿瘤的起始和生长。相反，异种移植中血管的减少会消除肿瘤中的自我更新细胞，并阻止肿瘤生长。我们提出脑癌干细胞维持于血管生态位内，而血管生态位是治疗方法的重要靶点。