[Migration and invasion of human hepatocellular carcinoma mediated by lung extracts].
OBJECTIVE
Invasion and metastasis are obstacles to successful treatment of hepatocellular carcinoma. Lung is the most common site of distant metastasis from hepatocellular carcinoma. In in vitro chemoinvasion assay that different tissue extracts from mice were used to induce human hepatocellular carcinoma cells with different metastatic potentials, lung extracts show the strongest inducing activity. This study was designed to investigate the mechanism of migration and invasion in human hepatocellular carcinoma with highly metastatic potential mediated by lung extracts from mice.


METHODS
The changes of cytoskeleton were tested using F-actin polymerization assay and flow cytometry (FCM). Correlation between matrix metalloproteinas-9 and F-actin was analyzed by fluorescence double staining in human hepatocellular carcinoma MHCC97-H cells induced by lung extracts.


RESULTS
When MHCC97-H cells were incubated with serum-free medium or spleen extracts, the cells showed elongated or polygonal morphology. When MHCC97-H cells were incubated with lung extracts, the formation of lamelliopodia or filopodia became more and more obvious and distinct as time increasing. Results of FCM showed that 1.9-fold increase in intracellular F-actin within 30s after MHCC97-H cells were incubated with lung extracts. Confocal laser scan microscopy of MHCC97-H cells stimulated in suspension showed intense F-actin staining in the periphery of the cells and redistribution of F-actin towards a leading edge. MMP-9 and F-actin were mainly localized in the perinuclear pool when the cells were incubated with serum-free medium. After stimulation with lung extracts, MMP-9 and F-actin were localized at the front of extending pseudopodia of MHCC97-H cells.


CONCLUSIONS
The mechanism that lung extracts promote migration and invasion of MHCC97-H may correlate with the pseudopodia formation and reorganization of MMP-9. Lung extracts may contribute to organ-specific metastasis of hepatocellular carcinoma.
Ji
Xue-Ning
XN
Key Laboratory of Carcinogenesis and Metastasis,Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032, P.R.China.
Ye
Sheng-Long
SL
Li
Yan
Y
Tian
Bo
B
Chen
Jie
J
Liu
Yin-Kun
YK
Tang
Zhao-You
ZY
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D002465:Cell Movement; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology*; D008168:Lung / Q000502:physiology*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009361:Neoplasm Invasiveness; D014020:Tissue Extracts / Q000494:pharmacology*
D014020:Tissue Extracts; D020780:Matrix Metalloproteinase 9