Chemokine CCL20 enhances the growth of HuH7 cells via phosphorylation of p44/42 MAPK in vitro.
CCR6 is the receptor of chemokine CCL20. In the present study, we demonstrated that the surface expression of CCR6 was enhanced on the human HCC cell lines (HuH7, PLC/PRF/5, and HepG2) especially on HuH7 cells, but not on HLE or HLF cells. These HCC cell lines (HuH7, PLC/PRF/5, and HepG2) especially the HuH7 cells secreted a significant amount of CCL20 spontaneously, whereas HLE or HLF did not. Stimulation by CCL20 up-regulated the mRNA expression of CCR6 in HuH7 cells and significantly enhanced the growth of HuH7 cells. CCL20-stimulated growth of HuH7 cells was abrogated by the inhibition of downstream signal transduction pathway mediated by p44/42 MAPK, but not by p38 MAPK or SAPK/JNK. CCR6 expression in human HCC tissues was confirmed by RT-PCR. These results indicate that the growth of a proportion of human HCC cells may be mediated by CCL20-CCR6 axis, like HuH7 cells, in an autocrine or paracrine manner.
Fujii
Hideki
H
Graduate School of Medical Science, Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Itoh
Yoshito
Y
Yamaguchi
Kanji
K
Yamauchi
Norihito
N
Harano
Yuichi
Y
Nakajima
Tomoki
T
Minami
Masahito
M
Okanoue
Takeshi
T
D001483:Base Sequence; D006528:Carcinoma, Hepatocellular; D002455:Cell Division / Q000502:physiology*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000235:genetics / Q000502:physiology; D054418:Chemokine CCL20; D019742:Chemokines, CC / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017931:DNA Primers; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D008113:Liver Neoplasms; D019402:Macrophage Inflammatory Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
C108355:CCL20 protein, human; D054418:Chemokine CCL20; D019742:Chemokines, CC; D017931:DNA Primers; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases