| 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 |
7
|
|
WOS Category
|
CLINICAL NEUROLOGY
ONCOLOGY
|
| Resource |
| Human and Animal Cells |
|
