Activation of chemokine receptor CXCR4 in malignant glioma cells promotes the production of vascular endothelial growth factor.
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, SDF1beta. 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.
Yang
Shi-xin
SX
Institute of Pathology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
Chen
Jian-hong
JH
Jiang
Xue-feng
XF
Jiang
Xiu-feng
XF
Wang
Qing-liang
QL
Chen
Zi-qiang
ZQ
Zhao
Wen
W
Feng
Yu-hui
YH
Xin
Rong
R
Shi
Jing-quan
JQ
Bian
Xiu-wu
XW
D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002465:Cell Movement; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000378:metabolism; D002633:Chemotaxis; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005910:Glioma / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008024:Ligands; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic; D012333:RNA, Messenger / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D014746:Vimentin / Q000378:metabolism
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D005904:Glial Fibrillary Acidic Protein; D008024:Ligands; D012333:RNA, Messenger; D019718:Receptors, CXCR4; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D014746:Vimentin; D002118:Calcium