Activation of chemokine receptor CXCR4 in malignant glioma cells promotes the production of vascular endothelial growth factor

被引:70
作者
Yang, SX
Chen, JH
Jiang, XF
Wang, QL
Chen, ZQ
Zhao, W
Feng, YH
Xin, R
Shi, JQ
Bian, XW [1 ]
机构
[1] Third Mil Med Univ, Southwest Hosp, Inst Pathol, Chongqing 400038, Peoples R China
[2] Third Mil Med Univ, Southwest Hosp, Dept Pharm, Chongqing 400038, Peoples R China
基金
中国国家自然科学基金;
关键词
glioma; chemokine receptor CXCR4; angiogenesis; vascular endothelial growth factor;
D O I
10.1016/j.bbrc.2005.07.113
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Numerous studies have showed that chemokine receptors, such as CXCR4, contribute to the growth and metastasis of a variety of malignant tumors. In this study, we investigated the role of CXCR4 in the production of angiogenic factor, vascular endothelial growth factor (VEGF), in various human glioma cells from astrocytic origin. The expression of CXCR4 mRNA and protein in three glioma cell lines, U87-MG, SHG-44, and CHG-5, was determined by RT-PCR and immunocytochemistry, respectively. The malignancies of three gliomas were evaluated by expression of glial fibrillary acidic protein and vimentin, the differentiation markers of astrocytic cells. The role of functional CXCR4 in tumor cell migration was studied with chemotaxis assay. Ca2+ mobilization and VEGF production were measured in the cells after stimulation with CXCR4 ligand, SDF1 beta. The results showed that the levels of functional CXCR4 expression at both mRNA and protein levels by several human glioma cell lines were correlated with the degree of differentiation of the tumor cells. Activation of CXCR4 induced glioma cell chemotaxis and could trigger the increase of intracellular [Ca2+](i). Such an activation could result in the increased production of VEGF by the stimulated tumor cells. Our results suggest that CXCR4 may contribute to the high level of VEGF produced by malignant glioma cells and thus constitute a therapeutic target for antiangiogenesis strategy. (c) 2005 Elsevier Inc. All rights reserved.
引用
收藏
页码:523 / 528
页数:6
相关论文
共 22 条
[1]   The significance of cancer cell expression of the chemokine receptor CXCR4 [J].
Balkwill, F .
SEMINARS IN CANCER BIOLOGY, 2004, 14 (03) :171-179
[2]   Inflammation and cancer: back to Virchow? [J].
Balkwill, F ;
Mantovani, A .
LANCET, 2001, 357 (9255) :539-545
[3]   Conditional switching of vascular endothelial growth factor (VEGF) expression in tumors: Induction of endothelial cell shedding and regression of hemangioblastoma-like vessels by VEGF withdrawal [J].
Benjamin, LE ;
Keshet, E .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (16) :8761-8766
[4]   Angiogenesis as an immunopharmacologic target in inflammation and cancer [J].
Bian, XW ;
Chen, JH ;
Jiang, XF ;
Bai, JS ;
Wang, QL ;
Zhang, X .
INTERNATIONAL IMMUNOPHARMACOLOGY, 2004, 4 (12) :1537-1547
[5]   A highly efficacious lymphocyte chemoattractant, stromal cell-derived factor 1 (SDF-1) [J].
Bleul, CC ;
Fuhlbrigge, RC ;
Casasnovas, JM ;
Aiuti, A ;
Springer, TA .
JOURNAL OF EXPERIMENTAL MEDICINE, 1996, 184 (03) :1101-1109
[6]  
Borgström P, 1998, PROSTATE, V35, P1
[7]  
Carmeliet P, 2000, ANN NY ACAD SCI, V902, P249
[8]  
Carmeliet P., 2000, ANN NY ACAD SCI, V902, P62
[9]   The expression of functional chemokine receptor CXCR4 is associated with the metastatic potential of human nasopharyngeal carcinoma [J].
Hu, JY ;
Deng, XY ;
Bian, XW ;
Li, GC ;
Tong, YQ ;
Li, YH ;
Wang, QL ;
Xin, R ;
He, XJ ;
Zhou, GH ;
Xie, PL ;
Li, YW ;
Wang, JM ;
Cao, Y .
CLINICAL CANCER RESEARCH, 2005, 11 (13) :4658-4665
[10]   Expression of functional CCR and CXCR chemokine receptors in podocytes [J].
Huber, TB ;
Reinhardt, HC ;
Exner, M ;
Burger, JA ;
Kerjaschki, D ;
Saleem, MA ;
Pavenstädt, H .
JOURNAL OF IMMUNOLOGY, 2002, 168 (12) :6244-6252