TY - JOUR
T1 - The Clinical Impact of Transcatheter Arterial Chemoembolization (TACE)-Induced c-Met Upregulation on TACE Refractoriness in Hepatocellular Carcinoma
AU - Kajihara, Jun
AU - Tomimaru, Yoshito
AU - Eguchi, Hidetoshi
AU - Yamada, Daisaku
AU - Wada, Hiroshi
AU - Tomokuni, Akira
AU - Asaoka, Tadafumi
AU - Kawamoto, Koichi
AU - Marubashi, Shigeru
AU - Nagano, Hiroaki
AU - Umeshita, Koji
AU - Doki, Yuichiro
AU - Mori, Masaki
PY - 2016/6/1
Y1 - 2016/6/1
N2 - Background: Transcatheter arterial chemoembolization (TACE) is a widely used and well-established treatment for hepatocellular carcinoma (HCC). However, TACE loses its therapeutic efficacy when performed repeatedly, a phenomenon termed TACE refractoriness. c-Met is associated with malignant potential and with resistance to anti-tumor therapies in some kinds of cancers. Aims: The aim of this study is to investigate the clinical impact of TACE on c-Met expression with the aim of understanding the mechanism underlying TACE refractoriness. Methods: The effect of TACE on the c-Met expression level was investigated in vitro in HCC cell lines, and it was shown that c-Met expression is upregulated in HCC cell lines cultured under hypoxia and/or exposed to chemotherapeutic agents. The in vitro results were validated using 82 clinical samples of HCC with and without preoperative TACE treatment. Results: c-Met upregulation was observed significantly more frequently in clinical samples of HCC that were treated with preoperative TACE than in samples with no TACE treatment. Increased c-Met expression was significantly associated with poor prognosis. Furthermore, the incidence of c-Met-positive expression was significantly higher in TACE-refractory HCC samples. Conclusions: TACE treatment upregulates c-Met expression in HCC and the upregulated c-Met expression may be responsible for TACE refractoriness.
AB - Background: Transcatheter arterial chemoembolization (TACE) is a widely used and well-established treatment for hepatocellular carcinoma (HCC). However, TACE loses its therapeutic efficacy when performed repeatedly, a phenomenon termed TACE refractoriness. c-Met is associated with malignant potential and with resistance to anti-tumor therapies in some kinds of cancers. Aims: The aim of this study is to investigate the clinical impact of TACE on c-Met expression with the aim of understanding the mechanism underlying TACE refractoriness. Methods: The effect of TACE on the c-Met expression level was investigated in vitro in HCC cell lines, and it was shown that c-Met expression is upregulated in HCC cell lines cultured under hypoxia and/or exposed to chemotherapeutic agents. The in vitro results were validated using 82 clinical samples of HCC with and without preoperative TACE treatment. Results: c-Met upregulation was observed significantly more frequently in clinical samples of HCC that were treated with preoperative TACE than in samples with no TACE treatment. Increased c-Met expression was significantly associated with poor prognosis. Furthermore, the incidence of c-Met-positive expression was significantly higher in TACE-refractory HCC samples. Conclusions: TACE treatment upregulates c-Met expression in HCC and the upregulated c-Met expression may be responsible for TACE refractoriness.
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U2 - 10.1007/s10620-015-4018-9
DO - 10.1007/s10620-015-4018-9
M3 - Article
C2 - 26725068
AN - SCOPUS:84952663020
VL - 61
SP - 1572
EP - 1581
JO - Digestive Diseases and Sciences
JF - Digestive Diseases and Sciences
SN - 0163-2116
IS - 6
ER -