Prostate tumor CXC-chemokine profile correlates with cell adhesion to endothelium and extracellular matrix

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• 作者：Tobias Engl ; Borna Relja ; Christa Blumenberg ; Iris Mü ; ller ; Eva M. Ringel ; Wolf-Dietrich Beecken ; Dietger Jonas and Roman A. Blaheta
• 关键词：Adhesion ; Chemokines ; Prostate carcinoma cells
• 刊名：Life Sciences
• 出版年：2006
• 出版时间：13 March 2006
• 年：2006
• 卷：78
• 期：16
• 页码：1784-1793
• 全文大小：399 K

文摘

Though chemokines of the CXC family are thought to play key roles in neoplastic transformation and tumor invasion, information about CXC chemokines in prostate cancer is sparse. To evaluate the involvement of CXC chemokines in prostate cancer, we analyzed the CXC coding mRNA of both chemokine ligands (CXCL) and chemokine receptors (CXCR), using the prostate carcinoma cell lines PC-3, DU-145 and LNCaP. CXCR proteins were further evaluated by Western blot, CXCR surface expression by flow cytometry and confocal microscopy. The expression pattern was correlated to adherence of the tumor cells to an endothelial cell monolayer or to extracellular matrix components. Based on growth and adhesion capacity, PC-3 and DU-145 were identified to be highly aggressive tumor cells (PC-3 > DU-145), whereas LNCaP belonged to the low aggressive phenotype. CXCL1, CXCL3, CXCL5 and CXCL6 mRNA, chemokines with pro-angiogenic activity, were strongly expressed in DU-145 and PC-3, but not in LNCaP. CXCR3 and CXCR4 surface level differed in the following order: LNCaP > DU-145 > PC-3. The differentiation factor, fatty acid valproic acid, induced intracellular CXCR accumulation. Therefore, prostate tumor malignancy might be accompanied by enhanced synthesis of angiogenesis stimulating CXC chemokines. Further, shifting CXCR3 and CXCR4 from the cell surface to the cytoplasm might activate pro-tumoral signalling events and indicate progression from a low to a highly aggressive phenotype.