Dissemination of hepatocellular carcinoma is mediated via chemokine receptor CXCR4.
In different tumour entities, expression of the chemokine receptor 4 (CXCR4) has been linked to tumour dissemination and poor prognosis. Therefore, we evaluated, if the expression of CXCR4 exerts similar effects in human hepatocellular carcinoma (HCC). Expression analysis and functional assays were performed in vitro to elucidate the impact of CXCL12 on human hepatoma cells lines. In addition, expression of CXCR4 was evaluated in 39 patients with HCC semiquantitatively and correlated with both, tumour and patients characteristics. Human HCC and hepatoma cell lines displayed variable intensities of CXCR4 expression. Loss of p53 function did not impact on CXCR4 expression. Exposure to CXCL12 mediated a perinuclear translocation of CXCR4 in Huh7/Hep3B cells and increased the invasive potential of Huh7 cells. In HCC patients, CXCR4 expression significantly correlated with progressed local tumours (T-status; P=0.006), lymphatic metastasis (N-status; P=0.005) and distant dissemination (M-status; P=0.009), as well as with a decreased 3-year-survival rate (P=0.01). In summary, strong expression of CXCR4 is significantly associated with progressed hepatocellular cancer.
Schimanski
C C
CC
First Department of Internal Medicine, Johannes Gutenberg University of Mainz, Langenbeckstrasse 1, 55101 Mainz, Germany. dr_schimanski@yahoo.de
Bahre
R
R
Gockel
I
I
Müller
A
A
Frerichs
K
K
Hörner
V
V
Teufel
A
A
Simiantonaki
N
N
Biesterfeld
S
S
Wehler
T
T
Schuler
M
M
Achenbach
T
T
Junginger
T
T
Galle
P R
PR
Moehler
M
M
D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000494:pharmacology; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011237:Predictive Value of Tests; D019718:Receptors, CXCR4 / Q000032:analysis / Q000378:metabolism*; D012680:Sensitivity and Specificity; D015996:Survival Rate; D014407:Tumor Cells, Cultured
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D019718:Receptors, CXCR4