TY  - JOUR
A1  - Engl, Tobias A.
A1  - Relja, Borna
A1  - Marian, Dana
A1  - Blumenberg, Christa
A1  - Müller, Iris
A1  - Beecken, Wolf-Dietrich
A1  - Jones, Jon
A1  - Ringel, Eva M.
A1  - Bereiter-Hahn, Jürgen
A1  - Jonas, Dietger
A1  - Blaheta, Roman A.
T1  - CXCR4 chemokine receptor mediates prostate tumor cell adhesion through alpha5 and beta3 integrins
T2  - Neoplasia
N2  - The mechanisms leading to prostate cancer metastasis are not understood completely. Although there is evidence that the CXC chemokine receptor (CXCR) 4 and its ligand CXCL12 may regulate tumor dissemination, their role in prostate cancer is controversial. We examined CXCR4 expression and functionality, and explored CXCL12-triggered adhesion of prostate tumor cells to human endothelium or to extracellular matrix proteins laminin, collagen, and fibronectin. Although little CXCR4 was expressed on LNCaP and DU-145 prostate tumor cells, CXCR4 was still active, enabling the cells to migrate toward a CXCL12 gradient. CXCL12 induced elevated adhesion to the endothelial cell monolayer and to immobilized fibronectin, laminin, and collagen. Anti-CXCR4 antibodies or CXCR4 knock out significantly impaired CXCL12-triggered tumor cell binding. The effects observed did not depend on CXCR4 surface expression level. Rather, CXCR4-mediated adhesion was established by alpha5 and beta3 integrin subunits and took place in the presence of reduced p38 and p38 phosphorylation. These data show that chemoattractive mechanisms are involved in adhesion processes of prostate cancer cells, and that binding of CXCL12 to its receptor leads to enhanced expression of alpha5 and beta3 integrins. The findings provide a link between chemokine receptor expression and integrin-triggered tumor dissemination.
KW  - Adhesion
KW  - CXCR4
KW  - CXCL12
KW  - integrins
KW  - prostate carcinoma cells
Y1  - 2014
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/75961
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-759610
SN  - 1476-5586
VL  - 8
IS  - 4
SP  - 290
EP  - 301
PB  - Neoplasia Press, Inc
ER  -