Expression analysis and potential functional role of the CXCR4 chemokine receptor in bladder cancer.
OBJECTIVE
Recent analysis gave evidence for the fact that the chemokine receptor CXCR4 is of functional significance in the multistep procedure of metastasis directing tumor cells to their metastatic target organs. In our study we investigated the expression of the CXCR4 receptor on bladder cancer cells and the functional activation of the CXCR4 receptor in bladder cancer cell lines regarding signal transduction pathways, which are involved in metastasis.


METHODS
Receptor transcript expression was analysed and quantified by reverse transcription PCR with RNA extracted from different samples of native human bladder cancer tissue, normal urothelium and the bladder cancer cell lines J82 and T24. Measurement of intracellular [Ca(++)](i) and analysis of intracellular stress fiber formation, chemotaxis, Matrigel invasion and proliferation were performed in the bladder cancer cell lines J82 and T24 upon stimulation with the specific agonist SDF-1.


RESULTS
Specific CXCR4 receptor transcripts were detected in normal urothelium, the bladder cancer cell lines J82 and T24 and in all bladder carcinoma specimens. We did not observe a quantitative correlation of transcript expression and tumor stage. While SDF-1 did not evoke increases in [Ca(++)](i) in bladder cancer cell lines, we observed a distinct rise in intracellular stress fiber formation, chemotactic activity, invasion through Matrigel coated membranes and cell growth upon stimulation with SDF-1, which was blocked in the presence of a specific CXCR4 receptor antibody.


CONCLUSIONS
Our results support that the chemokine receptor CXCR4 is an interesting candidate for the future investigation of metastasis of bladder cancer in vivo.
Eisenhardt
Andreas
A
Department of Pharmacology, University Hospital Essen, Hufelandstr. 55, 45122 Essen, Germany. Andreas.Eisenhardt@uni-essen.de
Frey
Ulrich
U
Tack
Monika
M
Rosskopf
Dieter
D
Lümmen
Gerd
G
Rübben
Herbert
H
Siffert
Winfried
W
D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000494:pharmacology; D006801:Humans; D012333:RNA, Messenger / Q000096:biosynthesis; D019718:Receptors, CXCR4 / Q000096:biosynthesis* / Q000235:genetics; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000209:etiology / Q000378:metabolism* / Q000473:pathology
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D012333:RNA, Messenger; D019718:Receptors, CXCR4