Chemokine expression in hepatocellular carcinoma versus colorectal liver metastases.
OBJECTIVE
To evaluate and compare the expression profiles of CXCL12 (SDF-1), CCL19 (MIP-3beta), CCL20 (MIP-3alpha) and CCL21 (6Ckine, Exodus2) and their receptors on RNA and protein levels in hepatocellular carcinoma (HCC) versus colorectal liver metastases (CRLM) and to elucidate their impact on the carcinogenesis and progression of malignant liver diseases.


METHODS
Chemokine expression was analyzed by RT-PCR and ELISA in 11 cases of HCC specimens and in 23 cases of CRLM and corresponding adjacent non-tumorous liver tissues, respectively. Expressions of their receptors CXCR4, CCR6 and CCR7 were analyzed by RT-PCR and Western blot analysis in the same cases of HCC and CRLM.


RESULTS
Significant up-regulation for CCL20/CCR6 was detected in both cancer types. Moreover, CCL20 demonstrated significant overexpression in CRLM in relation to the HCC tissues. Being significantly up-regulated only in CRLM, CXCR4 displayed an aberrant expression pattern with respect to the HCC tissues.


CONCLUSIONS
Correlation of CXCR4 expression with CRLM suggests CXCR4 as a potential predictive factor for CRLM. High level expression of CCL20 and its receptor CCR6 in HCC and CRLM with marked up-regulation of CCL20 in CRLM in relation to HCC tissues indicates involvement of the CCL20/CCR6 ligand-receptor pair in the carcinogenesis and progression of hepatic malignancies.
Rubie
Claudia
C
Department of General-, Visceral-, Vascular- and Paediatric Surgery, Universitatsklinikum des Saarlandes, Chirurgische Klinik, Gebaude 57, Homburg/Saar 66421, Germany. ca.labor@uniklinik-saarland.de
Frick
Vilma Oliveira
VO
Wagner
Mathias
M
Weber
Christina
C
Kruse
Bianca
B
Kempf
Katja
K
König
Jochen
J
Rau
Bettina
B
Schilling
Martin
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D054418:Chemokine CCL20; D054377:Chemokine CXCL12; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D019742:Chemokines, CC / Q000235:genetics / Q000378:metabolism; D019743:Chemokines, CXC / Q000235:genetics / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000556:secondary*; D019402:Macrophage Inflammatory Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000235:genetics / Q000473:pathology; D011237:Predictive Value of Tests; D054399:Receptors, CCR6; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
C108355:CCL20 protein, human; C106311:CCR6 protein, human; C515255:CXCL12 protein, human; D054418:Chemokine CCL20; D054377:Chemokine CXCL12; D018925:Chemokines; D019742:Chemokines, CC; D019743:Chemokines, CXC; D019402:Macrophage Inflammatory Proteins; D054399:Receptors, CCR6; D019718:Receptors, CXCR4; D019707:Receptors, Chemokine