Uchida Hiroki, Iwashita Yukio, Sasaki Atsushi, Shibata Kohei, Matsumoto Toshifumi, Ohta Masayuki, Kitano Seigo
Department of Surgery I, Oita University Faculty of Medicine, Oita, Japan.
J Gastroenterol Hepatol. 2006 Jan;21(1 Pt 1):161-8. doi: 10.1111/j.1440-1746.2005.04157.x.
Chemokines and their receptors have recently been shown to have major roles in cancer metastasis. The aim of this study was to determine whether the interaction between chemokine receptor 6 (CCR6) and its ligand, macrophage inflammatory protein-3 alpha (MIP-3alpha), correlates with metastasis of hepatocellular carcinoma (HCC).
To observe the reaction of CCR6 expressed cancer cells to MIP-3alpha stimulation, chemotactic and actin polymerization assays for both CCR6 high cells (HepG2) and CCR6 low cells (MCF-7) were performed. CCR6 mRNA levels in tumor specimens from 30 HCC patients were quantified by real-time polymerase chain reaction. Patients were classified into two groups, high (>or= 20 copies; n=10) CCR6 and low (<20 copies; n=20) CCR6 on the basis of CCR6 expression, and the groups were compared with respect to clinicopathological features.
When HepG2 cells (CCR6 high) were stimulated with MIP-3alpha, they migrated in a dose-dependent manner, and formation of pseudopodia was observed. These phenomena were not observed in the CCR6 low cells. The incidence of intrahepatic metastasis was higher in the high CCR6 expression group than in the low CCR6 expression group (P<0.05). Disease-free survival was significantly poorer in the high CCR6 expression group than in the low CCR6 expression group (P<0.05).
It was indicated that CCR6 might be associated with intrahepatic metastasis of HCC and might be able to become one of the prognostic factor after hepatic resection for HCC.
趋化因子及其受体最近被证明在癌症转移中起主要作用。本研究的目的是确定趋化因子受体6（CCR6）与其配体巨噬细胞炎性蛋白-3α（MIP-3α）之间的相互作用是否与肝细胞癌（HCC）的转移相关。
为观察表达CCR6的癌细胞对MIP-3α刺激的反应，对CCR6高表达细胞（HepG2）和CCR6低表达细胞（MCF-7）进行了趋化性和肌动蛋白聚合分析。通过实时聚合酶链反应对30例HCC患者肿瘤标本中的CCR6 mRNA水平进行定量。根据CCR6表达情况将患者分为两组，CCR6高表达组（≥20拷贝；n = 10）和CCR6低表达组（<20拷贝；n = 20），并比较两组的临床病理特征。
用MIP-3α刺激HepG2细胞（CCR6高表达）时，它们呈剂量依赖性迁移，并观察到伪足形成。在CCR6低表达细胞中未观察到这些现象。CCR6高表达组肝内转移发生率高于CCR6低表达组（P<0.05）。CCR6高表达组无病生存期明显短于CCR6低表达组（P<0.05）。
表明CCR6可能与HCC的肝内转移有关，并且可能成为HCC肝切除术后的预后因素之一。
