CXCR4 Chemokine Receptor Mediates Prostate Tumor Cell Adhesion through α5 and β3 Integrins

Neoplasia: An International Journal for Oncology Research

Christa Blumenberg¹  Eva M. Ringel¹  Roman A. Blaheta¹  Dana Marian¹  Boma Relja¹  Jon Jones¹  Tobias Engl¹  Iris Müller¹  Wolf-Dietrich Beecken¹  Dietger Jonas¹  Jürgen Bereiter-Hahn² 

[1] Zentrum der Chirurgie, Klinik für Urologie and Kinderurologie, Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany;lnstitut für Kinematische Zellforschung, Fachbereich Biowissenschaften, Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany;

关键词: Adhesion;    CXCR4;    CXCL12;    integrins;    prostate carcinoma cells;   

DOI  :  10.1593/neo.05694

来源: DOAJ

【 摘 要 】

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 CXCL 12-triggered tumor cell binding. The effects observed did not depend on CXCR4 surface expression level. Rather, CXCR4-mediated adhesion was established by α5 and β3 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 α5 and β3. The findings provide a link between chemokine receptor expression and integrin-triggered tumor dissemination.

【 授权许可】

Unknown