Department of Pathology, Shantou University Medical College, Guangdong, China.
Int J Cancer. 2010 Nov 15;127(10):2257-67. doi: 10.1002/ijc.25257.
Connective tissue growth factor (CTGF or CCN2) is a secreted protein that belongs to the CCN [cysteine-rich CYR61/CTGF/nephroblastoma-overexpressed gene] family. These proteins have been implicated in various biological processes, including stimulation of cell proliferation, migration, angiogenesis and tumorigenesis. In a previous study, we found that CTGF mRNA was elevated in primary gliomas, and a significant correlation existed between CTGF mRNA levels versus tumor grade, histology and patient survival. In this study, the role of CTGF in glioma tumorigenesis was explored. Forced expression of CTGF in glioblastoma multiforme (GBM) cells accelerated their growth in liquid culture and soft agar, stimulated cells migration in Boyden chamber assays and significantly increased their ability to form large, vascularized tumors in nude mice. CTGF induced the expression of the antiapoptotic proteins, Bcl-xl, Survivin and Flip. Overexpression of CTGF caused the U343 GBM cells to survive for longer than 40 days in serum-free medium and resist antitumor drugs including tumor necrosis factor (TNF), TNF-related apoptosis-inducing ligand, VELCADE (bortezomib, proteasome inhibitor) and temozolomide. Our data suggest that CTGF plays an important role in glioma progression, by supporting tumor cells survival and drug resistance.
结缔组织生长因子（CTGF 或 CCN2）是一种分泌蛋白，属于 CCN[富含半胱氨酸的 CYR61/CTGF/肾母细胞瘤过表达基因]家族。这些蛋白质与多种生物学过程有关，包括刺激细胞增殖、迁移、血管生成和肿瘤发生。在之前的研究中，我们发现 CTGF mRNA 在原发性神经胶质瘤中升高，并且 CTGF mRNA 水平与肿瘤分级、组织学和患者生存之间存在显著相关性。在这项研究中，探讨了 CTGF 在神经胶质瘤发生中的作用。在多形性胶质母细胞瘤（GBM）细胞中强制表达 CTGF 可加速其在液体培养和软琼脂中的生长，刺激细胞在 Boyden 室测定中的迁移，并显著增加其在裸鼠中形成大血管肿瘤的能力。CTGF 诱导抗凋亡蛋白 Bcl-xl、Survivin 和 Flip 的表达。CTGF 的过表达使 U343 GBM 细胞在无血清培养基中存活时间超过 40 天，并抵抗包括肿瘤坏死因子（TNF）、TNF 相关凋亡诱导配体、VELCADE（硼替佐米，蛋白酶体抑制剂）和替莫唑胺在内的抗肿瘤药物。我们的数据表明，CTGF 通过支持肿瘤细胞的存活和耐药性，在神经胶质瘤的进展中发挥重要作用。
