Transforming Growth Factor β1 Promotes Migration and Invasion of Human Hepatocellular Carcinoma Cells Via Up-Regulation of Connective Tissue Growth Factor.
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with a poor patient survival. Expression of TGF-β1 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-β1-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-β1, and that this effect is reversed by the specific inhibitor SB431542. Furthermore, TGF-β1 treatment up-regulated the expression of its own mRNA as well as the expression of CTGF mRNA. The TGF-β1-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-β1-induced tumorigenesis in experimental animals. In conclusion, TGF-β1 plays a critical role in HCC migration and invasion, and this effect is dependent on CTGF.
Department of Infectious Disease, Fuzhou General Hospital, Fuzhou, 350025, China. drliuhaizhou@163.com.
Haizhou
H
Liu
Department of Infectious Disease, Fuzhou General Hospital, Fuzhou, 350025, China.
Shaoyang
S
Wang
Department of Infectious Disease, Fuzhou General Hospital, Fuzhou, 350025, China.
Weimin
W
Ma
Department of Infectious Disease, Fuzhou General Hospital, Fuzhou, 350025, China.
Youguang
Y
Lu
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D055513:Connective Tissue Growth Factor / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009361:Neoplasm Invasiveness; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D015854:Up-Regulation
D016212:Transforming Growth Factor beta; D055513:Connective Tissue Growth Factor
CTGF; Cell migration; Hepatocellular carcinoma; Metastasis; TGF-β1