Hepatocytic precursor (stem-like) WB-F344 cells reduce tumorigenicity of hepatoma CBRH-7919 cells via TGF-beta/Smad pathway.
Hepatic stem cells (HSCs) are involved in repair of liver injury. Stem cells may have inhibitory effects on tumor cell growth and apoptosis. However, it is unknown whether HSCs regulate the biological functions of hepatocarcinoma cells, especially tumor cell growth and apoptosis. The present study was designed to determine the effects of hepatocytic precursor (stem-like) WB-F344 cells on the growth and apoptosis of hepatoma CBRH-7919 cells. Using a Transwell chamber culture system, we co-cultured WB-F344 cells and CBRH-7919 cells in serum-free conditioned medium at 3 different ratios: 1:1 (2 x 10(5): 2 x 10(5) cells/well), 1:5 (4 x 10(4): 2 x 10(5) cells/well), and 5:1 (2 x 10(5): 4 x 10(4) cells/well). We determined the effects of stem cells on tumor cells using in vivo xenograft assay in nude mice and determining gene expression by RT-PCR and Western blot analyses. With the increment proportion of the WB-F344 cells in the co-culture system, tumor formation was inhibited in nude mice. Moreover, down-regulation of bone morphogenetic protein 4 (BMP4), Bcl-2, and c-Myc and upregulation of PTEN also occurred along with the inhibitory effects. Western blotting showed that the TGF-beta/Smad pathway played a prominent role in tumor inhibition, which may have been mediated by the cytokines released from the stem cells. In conclusion, hepatocytic precursor (stem-like) WB-F344 cells inhibit the tumorigenicity of hepatoma CBRH-7919 cells, and the effect is mediated by TGF-beta/Smad signaling pathway.
Li
Wei-Qing
WQ
Department of Pathology, Changzheng Hospital, The Second Military Medical University, Shanghai 200003, PR China.
Li
Yi-Ming
YM
Guo
Jia
J
Liu
Yu-Ming
YM
Yang
Xiao-Qun
XQ
Ge
Hui-Juan
HJ
Xu
Yi
Y
Liu
Hui-Min
HM
He
Jin
J
Yu
Hong-Yu
HY
D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D049109:Cell Proliferation; D018920:Coculture Techniques; D005434:Flow Cytometry; D022781:Hepatocytes / Q000378:metabolism / Q000637:transplantation*; D008114:Liver Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011916:Rats, Inbred F344; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D051901:Smad4 Protein / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells / Q000378:metabolism*; D015996:Survival Rate; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
D012333:RNA, Messenger; D051901:Smad4 Protein; D016212:Transforming Growth Factor beta