Experimental study on enhancement of the metastatic potential of portal vein tumor thrombus-originated hepatocellular carcinoma cells using portal vein serum.
OBJECTIVE
Portal vein metastasis of hepatocellular carcinoma (HCC) results in a poor prognosis and seriously affects the survival rate of patients. The mechanism underlying the formation of portal vein tumor thrombus (PVTT) is complex and is not yet fully understood. This study was conducted to investigate the impact of portal vein blood on the proliferation, metastasis, invasion and apoptosis of PVTT cells and to explore its possible mechanisms, which was expected to lay a foundation for ascertaining the mechanism underlying the portal vein metastasis of HCC.


METHODS
Peripheral blood and portal vein blood were collected from patients with HCC, and the sera from these two sources were used to culture the PVTT-originated HCC cell line CSQT-2. The cells were collected after 24 h, and flow cytometry was performed to detect cell proliferation, cell cycle stages and apoptosis. Transwell migration and invasion assays were applied to detect the metastasis and invasion of the cells in each group. The changes in the expression of MMP-2 and MMP-9 in cells were detected via Western blotting. The contents of IL-12, IFN-γ, IL-1β, IL-2 and TNF-α in the two groups of sera were quantified using corresponding kits.


RESULTS
Compared with the group of cells cultured with peripheral serum, the cells cultured with portal vein serum showed significantly lower apoptosis (P<0.01), significantly enhanced cell metastasis and invasion (P<0.01), whereas cell proliferation and the stages of the cell cycle did not differ significantly (P>0.05). A significantly increased expression level of MMP-2 has been observed in tumor cells treated portal vein serum. In addition, compared with peripheral serum, the content of IL-12 was significantly decreased in portal vein serum (P<0.05), while the contents of IFN-γ, IL-1β, IL-2, and TNF-α did not differ significantly (P>0.05).


CONCLUSIONS
Portal vein serum from HCC patients could inhibit the apoptosis of PVTT-originated HCC cells and promote cell metastasis and invasion. This effect may be related to the lower level of IL-12 in portal vein serum.
1 Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China ; 2 Department of Hepatobiliary Surgery, General Hospital of Shenyang Military Area Command, Liaoning 110016, China ; 3 Changhai Hospital, Second Military Medical University, Shanghai 200433, China ; 4 International Cooperation Laboratory on Signal Transduction of Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai 200438, China.
Yufu
Y
Tang
1 Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China ; 2 Department of Hepatobiliary Surgery, General Hospital of Shenyang Military Area Command, Liaoning 110016, China ; 3 Changhai Hospital, Second Military Medical University, Shanghai 200433, China ; 4 International Cooperation Laboratory on Signal Transduction of Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai 200438, China.
Hongming
H
Yu
1 Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China ; 2 Department of Hepatobiliary Surgery, General Hospital of Shenyang Military Area Command, Liaoning 110016, China ; 3 Changhai Hospital, Second Military Medical University, Shanghai 200433, China ; 4 International Cooperation Laboratory on Signal Transduction of Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai 200438, China.
Long
L
Zhang
1 Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China ; 2 Department of Hepatobiliary Surgery, General Hospital of Shenyang Military Area Command, Liaoning 110016, China ; 3 Changhai Hospital, Second Military Medical University, Shanghai 200433, China ; 4 International Cooperation Laboratory on Signal Transduction of Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai 200438, China.
Kang
K
Wang
1 Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China ; 2 Department of Hepatobiliary Surgery, General Hospital of Shenyang Military Area Command, Liaoning 110016, China ; 3 Changhai Hospital, Second Military Medical University, Shanghai 200433, China ; 4 International Cooperation Laboratory on Signal Transduction of Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai 200438, China.
Weixing
W
Guo
1 Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China ; 2 Department of Hepatobiliary Surgery, General Hospital of Shenyang Military Area Command, Liaoning 110016, China ; 3 Changhai Hospital, Second Military Medical University, Shanghai 200433, China ; 4 International Cooperation Laboratory on Signal Transduction of Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai 200438, China.
Jie
J
Shi
1 Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China ; 2 Department of Hepatobiliary Surgery, General Hospital of Shenyang Military Area Command, Liaoning 110016, China ; 3 Changhai Hospital, Second Military Medical University, Shanghai 200433, China ; 4 International Cooperation Laboratory on Signal Transduction of Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai 200438, China.
Shupeng
S
Liu
1 Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China ; 2 Department of Hepatobiliary Surgery, General Hospital of Shenyang Military Area Command, Liaoning 110016, China ; 3 Changhai Hospital, Second Military Medical University, Shanghai 200433, China ; 4 International Cooperation Laboratory on Signal Transduction of Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai 200438, China.
Mengchao
M
Wu
1 Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China ; 2 Department of Hepatobiliary Surgery, General Hospital of Shenyang Military Area Command, Liaoning 110016, China ; 3 Changhai Hospital, Second Military Medical University, Shanghai 200433, China ; 4 International Cooperation Laboratory on Signal Transduction of Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai 200438, China.
Hongyang
H
Wang
1 Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China ; 2 Department of Hepatobiliary Surgery, General Hospital of Shenyang Military Area Command, Liaoning 110016, China ; 3 Changhai Hospital, Second Military Medical University, Shanghai 200433, China ; 4 International Cooperation Laboratory on Signal Transduction of Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai 200438, China.
Shuqun
S
Cheng
Hepatocellular carcinoma (HCC); metastasis; portal vein; portal vein tumor thrombus (PVTT)