Vascular heterogeneity and targeting: the role of YKL-40 in glioblastoma vascularization.
Vascular heterogeneity and targeting: the role of YKL-40 in glioblastoma vascularization.
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DOI：
10.18632/oncotarget.5943
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发表时间：
2015-12-01
期刊：
影响因子：
--
通讯作者：
Schwartz LM
中科院分区：
文献类型：
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作者：
Shao R;Taylor SL;Oh DS;Schwartz LM
恶性胶质母细胞瘤是一种高度恶性的脑肿瘤，具有广泛和异常的肿瘤血管系统，包括多种类型的血管。本文综述了近年来血管生成因子YKL-40 （CHI3L1）作用于胶质母细胞瘤干细胞样细胞（GSCs），驱动两种主要形式的肿瘤血管形成：血管生成和血管生成模拟（VM）。GSCs具有多能细胞，能够转分化为血管周细胞或平滑肌细胞（PC/SMCs），这些细胞可以与内皮细胞（ECs）协调促进血管生成，也可以在没有ECs的情况下通过VM组装形成血液灌注通道。GBMs表达高水平的YKL-40，驱动不同的信号级联，介导这些不同微血管循环的形成。尽管多种靶向血管生成的抗肿瘤药物已经证明对患者有短暂的益处，但它们往往不能限制肿瘤的生长，这强调了对其他治疗工具的需求。我们建议，靶向YKL-40可能会补充传统的抗血管生成治疗，为GBM和其他几种类型的实体瘤患者提供实质性的临床益处。
Malignant glioblastomas (GBM) are highly malignant brain tumors that have extensive and aberrant tumor vasculature, including multiple types of vessels. This review focuses on recent discoveries that the angiogenic factor YKL-40 (CHI3L1) acts on glioblastoma-stem like cells (GSCs) to drive the formation of two major forms of tumor vascularization: angiogenesis and vasculogenic mimicry (VM). GSCs possess multipotent cells able to transdifferentiate into vascular pericytes or smooth muscle cells (PC/SMCs) that either coordinate with endothelial cells (ECs) to facilitate angiogenesis or assemble in the absence of ECs to form blood-perfused channels via VM. GBMs express high levels of YKL-40 that drives the divergent signaling cascades to mediate the formation of these distinct microvascular circulations. Although a variety of anti-tumor agents that target angiogenesis have demonstrated transient benefits for patients, they often fail to restrict tumor growth, which underscores the need for additional therapeutic tools. We propose that targeting YKL-40 may compliment conventional anti-angiogenic therapies to provide a substantial clinical benefit to patients with GBM and several other types of solid tumors.