Overexpression of cortactin is involved in motility and metastasis of hepatocellular carcinoma.
OBJECTIVE
The molecular basis of the metastasis of hepatocellular carcinoma (HCC) is not fully understood. The aim of this study was to elucidate the crucial genes involved in metastasis of HCC.


METHODS
We compared expression profiles among highly metastatic HCC cell lines and non-metastatic HCC cell lines by using oligonucleotide array to identify genes associated with metastasis. We further investigated the effect of identified gene on cell motility and metastasis in vitro and in vivo. Finally, we examined immunohistochemistry in human tissue samples.


RESULTS
We identified 39 genes whose expression levels were significantly correlated with metastatic ability (P<0.05). Of these genes, we further investigated cortactin, because this cortical actin-associated protein is a substrate of Src, whose activation has been shown to be involved in HCC cell migration and metastasis. Overexpression of cortactin in a non-metastatic HCC cell line increased cell motility, and resulted in metastasis in an orthotopic model. Furthermore, immunohistochemical expression of cortactin revealed its significant overexpression in HCC with intrahepatic metastasis compared with HCC without intrahepatic metastasis (P<0.005).


CONCLUSIONS
Overexpression of cortactin may play a role in the metastasis of HCC by influencing cell motility, and cortactin could be a sensitive marker for HCC with intrahepatic metastasis.
Chuma
Makoto
M
Pathology Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
Sakamoto
Michiie
M
Yasuda
Jun
J
Fujii
Gen
G
Nakanishi
Kazuaki
K
Tsuchiya
Akira
A
Ohta
Tsutomu
T
Asaka
Masahiro
M
Hirohashi
Setsuo
S
D000465:Algorithms; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000503:physiopathology* / Q000556:secondary*; D045744:Cell Line, Tumor; D002465:Cell Movement; D051356:Cortactin; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology* / Q000556:secondary*; D008114:Liver Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D008840:Microfilament Proteins / Q000378:metabolism*
C495868:CTTN protein, human; D051356:Cortactin; C495869:Cttn protein, mouse; D008840:Microfilament Proteins