RRC ID 44860
Author Uemae Y, Ishikawa E, Osuka S, Matsuda M, Sakamoto N, Takano S, Nakai K, Yamamoto T, Matsumura A.
Title CXCL12 secreted from glioma stem cells regulates their proliferation.
Journal J Neurooncol
Abstract Emerging evidence suggests that the chemokine CXCL12 and its receptor CXCR4, which are expressed by glioma stem cells (GSCs), play an important role in tumorigenesis. To provide evidence for establishing a new therapy targeting the CXCL12/CXCR4 pathway, we investigated whether CXCL12 secreted from GSCs contributed to their proliferation and promoted angiogenesis in murine GSCs. Angiogenetic functions and proliferation of GSCs with or without CXCL12 inhibitors were evaluated in an in vitro model using tube formation assays, RT-PCR, and proliferation, as well as in an in vivo syngenic model. In endothelial culture, the morphology and gene expression of GSCs changed from stem cell-like characteristics to endothelial cell-like features. CXCL12 expression increased in endothelial cell-like GSCs. CXCL12 blockage with siRNA or shRNA markedly inhibited cell proliferation in vitro. CXCL12 knockdown with shRNA also inhibited tumor growth in vivo. On the other hand, CXCL12/CXCR4 blockage affected neither tube formation in vitro nor angiogenesis in vivo. The CXCL12 secreted from GSCs (autocrine/paracrine CXCL12) regulates their proliferation, but probably not angiogenesis.
Volume 117(1)
Pages 43-51
Published 2014-3
DOI 10.1007/s11060-014-1364-y
PMID 24442483
MeSH Animals Cell Line, Tumor Cell Proliferation* Chemokine CXCL12 / antagonists & inhibitors Chemokine CXCL12 / genetics Chemokine CXCL12 / metabolism* Endothelial Cells / pathology Endothelial Cells / physiology Enzyme-Linked Immunosorbent Assay Gene Knockdown Techniques Glioma / metabolism* Glioma / pathology Glioma / physiopathology* Immunohistochemistry Male Mice Mice, Inbred C57BL Neoplasm Transplantation Neoplastic Stem Cells / metabolism* Neoplastic Stem Cells / pathology Neoplastic Stem Cells / physiology* Neovascularization, Pathologic / pathology Neovascularization, Pathologic / physiopathology RNA, Small Interfering Real-Time Polymerase Chain Reaction Receptors, CXCR4 / antagonists & inhibitors Receptors, CXCR4 / genetics Receptors, CXCR4 / metabolism
IF 3.129
Times Cited 11
Human and Animal Cells