Shao Rong, Taylor Sherry L, Oh Dennis S, Schwartz Lawrence M
Department of Biology, University of Massachusetts, Amherst, MA, USA.
Molecular and Cellular Biology Program, Morrill Science Center, University of Massachusetts, Amherst, MA, USA.
Oncotarget. 2015 Dec 1;6(38):40507-18. doi: 10.18632/oncotarget.5943.
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.
恶性胶质母细胞瘤（GBM）是高度恶性的脑肿瘤，具有广泛且异常的肿瘤血管系统，包括多种类型的血管。本综述聚焦于近期的发现，即血管生成因子YKL-40（CHI3L1）作用于胶质母细胞瘤干细胞样细胞（GSCs），以驱动肿瘤血管生成的两种主要形式：血管生成和血管生成拟态（VM）。GSCs拥有多能细胞，能够转分化为血管周细胞或平滑肌细胞（PC/SMCs），这些细胞要么与内皮细胞（ECs）协同促进血管生成，要么在没有ECs的情况下聚集，通过VM形成血液灌注通道。GBM表达高水平的YKL-40，其驱动不同的信号级联反应，以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显示对患者有短暂益处，但它们往往无法限制肿瘤生长，这凸显了对额外治疗工具的需求。我们提出，靶向YKL-40可能补充传统的抗血管生成疗法，为GBM患者和其他几种实体瘤患者带来显著的临床益处。
