Enhanced expression and clinical significance of CC-chemokine MIP-3 alpha in hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is one of the most frequent visceral neoplasms worldwide. Using RT-PCR, ELISA, microdissection and immunohistochemistry, we investigated the expression profiles of CCL19, CCL20, CCL21 and CXCL12 and their receptors in tumourous and tumour neighbouring tissues from patients with HCC and in nonmalignant liver lesions, respectively. All chemokines were found to be expressed in normal liver and HCC tissues, yet CCL20 was the only chemokine showing significant upregulation in HCC tissues. Clinicopathological analysis revealed a distinct increase in CCL20 expression rates in HCC tissues of grade III tumours in comparison to HCC tissues from grade II tumours. On mRNA level, only chemokine receptor CCR6 revealed significant upregulation in HCC tissues. However, immunohistochemical studies indicated a marked CCR6 expression accumulated in a streak of normal cells along the tumour invasion front in all our HCC specimens which could provide a stimulative signal for the tumour to further expand. The present findings show significant overexpression of CCL20 in the tumour tissues and marked overexpression of the corresponding receptor CCR6 in the tumour invasion front of HCC patients in comparison to normal liver. Moreover, CCL20 expression was found to correlate with tumour grade and therefore, we suggest that the CCL20/CCR6 system may be involved in hepatocarcinogenesis.
Rubie
C
C
Department of General-, Visceral-, Vascular- and Paediatric Surgery, University of the Saarland, Homburg/Saar, Germany. ca.labor@uniklinik-saarland.de
Frick
V O
VO
Wagner
M
M
Rau
B
B
Weber
C
C
Kruse
B
B
Kempf
K
K
Tilton
B
B
König
J
J
Schilling
M
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D054418:Chemokine CCL20; D019742:Chemokines, CC / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D008297:Male; D008875:Middle Aged; D054399:Receptors, CCR6; D019707:Receptors, Chemokine / Q000502:physiology
D014408:Biomarkers, Tumor; C108355:CCL20 protein, human; C106311:CCR6 protein, human; D054418:Chemokine CCL20; D019742:Chemokines, CC; D019402:Macrophage Inflammatory Proteins; D054399:Receptors, CCR6; D019707:Receptors, Chemokine