Department of Vascular Biology, Graduate School of Dental Medicine, N13 W7, University of Hokkaido, Sapporo, Hokkaido 060-8586, Japan.
Br J Cancer. 2012 Mar 13;106(6):1214-23. doi: 10.1038/bjc.2012.59. Epub 2012 Feb 28.
We isolated tumour endothelial cells (TECs), demonstrated their abnormalities, compared gene expression profiles of TECs and normal endothelial cells (NECs) by microarray analysis and identified several genes upregulated in TECs. We focused on the gene encoding biglycan, a small leucine-rich repeat proteoglycan. No report is available on biglycan expression or function in TECs.
The NEC and TEC were isolated. We investigated the biglycan expression and function in TECs. Western blotting analysis of biglycan was performed on sera from cancer patients.
Biglycan expression levels were higher in TECs than in NECs. Biglycan knockdown inhibited cell migration and caused morphological changes in TECs. Furthermore, immunostaining revealed strong biglycan expression in vivo in human tumour vessels, as in mouse TECs. Biglycan was detected in the sera of cancer patients but was hardly detected in those of healthy volunteers.
These findings suggested that biglycan is a novel TEC marker and a target for anti-angiogenic therapy.
我们分离了肿瘤内皮细胞（TECs），通过微阵列分析比较了 TECs 和正常内皮细胞（NECs）的基因表达谱，并鉴定出了 TECs 中上调的几个基因。我们专注于编码 biglycan 的基因，biglycan 是一种小型富含亮氨酸的重复蛋白聚糖。目前尚无关于 TECs 中 biglycan 表达或功能的报告。
分离 NEC 和 TEC。我们研究了 TEC 中的 biglycan 表达和功能。对癌症患者的血清进行 biglycan 的 Western blot 分析。
TECs 中的 biglycan 表达水平高于 NECs。biglycan 敲低抑制了 TEC 的迁移，并导致其形态发生变化。此外，免疫染色显示在人类肿瘤血管中体内存在强烈的 biglycan 表达，与小鼠 TECs 中的表达情况相同。在癌症患者的血清中检测到了 biglycan，但在健康志愿者的血清中几乎检测不到。
这些发现表明 biglycan 是一种新型的 TEC 标志物，也是抗血管生成治疗的一个靶点。
