Chemokine receptor CCR6 as a prognostic factor after hepatic resection for hepatocellular carcinoma.
OBJECTIVE
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).


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Uchida
Hiroki
H
Department of Surgery I, Oita University Faculty of Medicine, Oita, Japan. ucchy@med.oita-u.ac.jp
Iwashita
Yukio
Y
Sasaki
Atsushi
A
Shibata
Kohei
K
Matsumoto
Toshifumi
T
Ohta
Masayuki
M
Kitano
Seigo
S
D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D045744:Cell Line, Tumor; D002633:Chemotaxis; D003599:Cytoskeleton / Q000187:drug effects; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005260:Female; D006498:Hepatectomy; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D019402:Macrophage Inflammatory Proteins / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011554:Pseudopodia; D012333:RNA, Messenger / Q000378:metabolism; D054399:Receptors, CCR6; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism*
D014408:Biomarkers, Tumor; C106311:CCR6 protein, human; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger; D054399:Receptors, CCR6; D019707:Receptors, Chemokine