Abstract
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. 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. 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). 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.
| Original language | English |
|---|---|
| Pages (from-to) | 629-636 |
| Number of pages | 8 |
| Journal | Journal of Hepatology |
| Volume | 41 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 2004 Oct |
Fingerprint
Keywords
- Cell motility
- Cortactin
- Hepatocellular carcinoma
- Intrahepatic metastasis
- Oligonucleotide array
- Short interfering RNA molecule
ASJC Scopus subject areas
- Gastroenterology
Cite this
Overexpression of cortactin is involved in motility and metastasis of hepatocellular carcinoma. / Chuma, Makoto; Sakamoto, Michiie; Yasuda, Jun; Fujii, Gen; Nakanishi, Kazuaki; Tsuchiya, Akira; Ohta, Tsutomu; Asaka, Masahiro; Hirohashi, Setsuo.
In: Journal of Hepatology, Vol. 41, No. 4, 10.2004, p. 629-636.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Overexpression of cortactin is involved in motility and metastasis of hepatocellular carcinoma
AU - Chuma, Makoto
AU - Sakamoto, Michiie
AU - Yasuda, Jun
AU - Fujii, Gen
AU - Nakanishi, Kazuaki
AU - Tsuchiya, Akira
AU - Ohta, Tsutomu
AU - Asaka, Masahiro
AU - Hirohashi, Setsuo
PY - 2004/10
Y1 - 2004/10
N2 - 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. 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. 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). 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.
AB - 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. 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. 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). 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.
KW - Cell motility
KW - Cortactin
KW - Hepatocellular carcinoma
KW - Intrahepatic metastasis
KW - Oligonucleotide array
KW - Short interfering RNA molecule
UR - http://www.scopus.com/inward/record.url?scp=4644271628&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=4644271628&partnerID=8YFLogxK
U2 - 10.1016/j.jhep.2004.06.018
DO - 10.1016/j.jhep.2004.06.018
M3 - Article
C2 - 15464244
AN - SCOPUS:4644271628
VL - 41
SP - 629
EP - 636
JO - Journal of Hepatology
JF - Journal of Hepatology
SN - 0168-8278
IS - 4
ER -