Connective tissue growth factor associated with oncogenic activities and drug resistance in glioblastoma multiforme.
Connective tissue growth factor associated with oncogenic activities and drug resistance in glioblastoma multiforme.
复制标题
DOI：
10.1002/ijc.25257
复制
发表时间：
2010-11-15
影响因子：
6.4
通讯作者：
Koeffler, H. Phillip
中科院分区：
文献类型：
--
作者：
Yin, Dong;Chen, Weikai;O'Kelly, James;Lu, Daning;Ham, Michelle;Doan, Ngan B.;Xie, Dong;Wang, Charles;Vadgama, Jay;Said, Jonathan W.;Black, Keith L.;Koeffler, H. Phillip
结缔组织生长因子（CTGF或CCN 2）是属于CCN [富含半胱氨酸的CYR 61/结缔组织生长因子/肾母细胞瘤过表达基因]家族的分泌蛋白。这些蛋白质涉及各种生物过程，包括刺激细胞增殖、迁移、血管生成和肿瘤发生。在以前的研究中，我们发现CTGF mRNA在原发性胶质瘤中升高，CTGF mRNA水平与肿瘤分级、组织学和患者生存率之间存在显著相关性。本研究探讨CTGF在胶质瘤发生中的作用。CTGF在多形性胶质母细胞瘤（GBM）细胞中的强制表达加速了它们在液体培养和软琼脂中的生长，刺激了Boyden室测定中的细胞迁移，并显著增加了它们在裸鼠中形成大的血管化肿瘤的能力。CTGF诱导抗凋亡蛋白Bcl-xl、Survivin和Flip的表达。CTGF的过表达导致U343 GBM细胞在无血清培养基中存活超过40天，并对抗肿瘤药物，包括肿瘤坏死因子（TNF）、TNF相关凋亡诱导配体（TRAIL）、万珂（硼替佐米，蛋白酶体抑制剂）和替莫唑胺。我们的数据表明，CTGF通过支持肿瘤细胞的存活和耐药性，在胶质瘤进展中起着重要作用。
Connective tissue growth factor (CTGF or CCN2) is a secreted protein that belongs to the CCN [cysteine-rich CYR61/connective tissue growth factor/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 the present 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 anti-apoptotic proteins, Bcl-xl, Survivin, and Flip. Over-expression of CTGF caused the U343 GBM cells to survive for longer than 40 days in serum-free medium and resist anti-tumor drugs including tumor necrosis factor (TNF), TNF-related apoptosis-inducing ligand (TRAIL), 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.
登录
查看更多内容
影响因子：
8
作者：
Duerr, EM;Rollbrocker, B;von Deimling, A
通讯作者：
von Deimling, A
影响因子：
4.4
作者：
Demuth T;Rennert JL;Hoelzinger DB;Reavie LB;Nakada M;Beaudry C;Nakada S;Anderson EM;Henrichs AN;McDonough WS;Holz D;Joy A;Lin R;Pan KH;Lih CJ;Cohen SN;Berens ME
通讯作者：
Berens ME
影响因子：
5.8
作者：
Planque N;Perbal B
通讯作者：
Perbal B
影响因子：
4.6
作者：
Mercurio, S;Latinkic, B;Smith, JC
通讯作者：
Smith, JC
影响因子：
3.9
作者：
Jiang, WG;Watkins, G;Mansel, RE
通讯作者：
Mansel, RE