Transforming Growth Factor β1 Promotes Migration and Invasion of Human Hepatocellular Carcinoma Cells Via Up-Regulation of Connective Tissue Growth Factor

被引:8
作者
Liu, Haizhou [1 ]
Wang, Shaoyang [1 ]
Ma, Weimin [1 ]
Lu, Youguang [1 ]
机构
[1] Fuzhou Gen Hosp, Dept Infect Dis, Fuzhou 350025, Peoples R China
关键词
TGF-beta; 1; CTGF; Cell migration; Metastasis; Hepatocellular carcinoma; FACTOR CTGF/CCN2; PROGRESSION; METASTASIS; INHIBITION; EXPRESSION; KINASE;
D O I
10.1007/s12013-015-0693-6
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with a poor patient survival. Expression of TGF-beta 1 is up-regulated in HCC and is thought to play a crucial role in the occurrence and development of HCC. However, the mechanism of TGF-beta 1-mediated facilitation of malignant growth and invasion remains unclear, although some previous studies highlighted a potential involvement of the connective tissue growth factor (CTGF). Here we demonstrate that the in vitro migration of the HCC cell line SMMC-7721 is increased in the presence of recombinant TGF-beta 1, and that this effect is reversed by the specific inhibitor SB431542. Furthermore, TGF-beta 1 treatment up-regulated the expression of its own mRNA as well as the expression of CTGF mRNA. The TGF-beta 1-stimulated migration of SMMC-7721 cells was diminished by siRNA silencing of CTGF. These in vitro observations were validated in a murine xenograft model. In particular, silencing of CTFG diminished the TGF-beta 1-induced tumorigenesis in experimental animals. In conclusion, TGF-beta 1 plays a critical role in HCC migration and invasion, and this effect is dependent on CTGF.
引用
收藏
页码:775 / 781
页数:7
相关论文
共 35 条
[11]   Transforming growth factor β and atherosclerosis:: So far, so good for the protective cytokine hypothesis [J].
Grainger, DJ .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2004, 24 (03) :399-404
[12]   Role of transforming growth factor-beta1-smad signal transduction pathway in patients with hepatocellular carcinoma [J].
Ji, Guo-Zhong ;
Wang, Xue-Hao ;
Miao, Lin ;
Liu, Zheng ;
Zhang, Ping ;
Zhang, Fa-Ming ;
Yang, Jian-Bing .
WORLD JOURNAL OF GASTROENTEROLOGY, 2006, 12 (04) :644-648
[13]   Recurrence or metastasis of HCC: predictors, early detection and experimental antiangiogenic therapy [J].
Jiang, YF ;
Yang, ZH ;
Hu, JQ .
WORLD JOURNAL OF GASTROENTEROLOGY, 2000, 6 (01) :61-65
[14]   Fibroblasts in cancer [J].
Kalluri, R ;
Zeisberg, M .
NATURE REVIEWS CANCER, 2006, 6 (05) :392-401
[15]  
Kong Dejuan, 2011, Cancers (Basel), V3, P716, DOI 10.3390/cancers30100716
[16]  
Kothapalli D, 2000, J CELL PHYSIOL, V182, P119, DOI 10.1002/(SICI)1097-4652(200001)182:1<119::AID-JCP13>3.3.CO
[17]  
2-W
[18]   Pentoxifylline attenuates tubulointerstitial fibrosis by blocking Smad3/4-activated transcription and profibrogenic effects of connective tissue growth factor [J].
Lin, SL ;
Chen, RH ;
Chen, YM ;
Chiang, WC ;
Lai, CF ;
Wu, KD ;
Tsai, TJ .
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2005, 16 (09) :2702-2713
[19]   Inhibition of integrin-linked kinase via a siRNA expression plasmid attenuates connective tissue growth factor-induced human proximal tubular epithelial cells to mesenchymal transition [J].
Liu, Bi-Cheng ;
Li, Min-Xia ;
Zhang, Jian-Dong ;
Liu, Xiao-Cong ;
Zhang, Xiao-Liang ;
Phillips, Aled O. .
AMERICAN JOURNAL OF NEPHROLOGY, 2008, 28 (01) :143-151
[20]   RETRACTED: Restoration of Transforming Growth Factor-β Receptor II Expression in Colon Cancer Cells with Microsatellite Instability Increases Metastatic Potential in Vivo (Retracted Article) [J].
Liu, Xiao-Qiong ;
Rajput, Ashwani ;
Geng, Liying ;
Ongchin, Melanie ;
Chaudhuri, Anathbandhu ;
Wang, Jing .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2011, 286 (18) :16082-16090