Neuronal and glioma-derived stem cell factor induces angiogenesis within the brain.
Stem cell factor (SCF) is overexpressed by neurons following brain injury as well as by glioma cells; however, its role in gliomagenesis remains unclear. Here, we demonstrate that SCF directly activates brain microvascular endothelial cells (ECs) in vitro and induces a potent angiogenic response in vivo. Primary human gliomas express SCF in a grade-dependent manner and induce normal neurons to express SCF in brain regions infiltrated by glioma cells, areas that colocalize with prominent angiogenesis. Downregulation of SCF inhibits tumor-mediated angiogenesis and glioma growth in vivo, whereas overexpression of SCF is associated with shorter survival in patients with malignant gliomas. Thus, the SCF/c-Kit pathway plays an important role in tumor- and normal host cell-induced angiogenesis within the brain.
Sun
Lixin
L
Neuro-Oncology Branch, National Cancer Institute/National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA.
Hui
Ai-Min
AM
Su
Qin
Q
Vortmeyer
Alexander
A
Kotliarov
Yuri
Y
Pastorino
Sandra
S
Passaniti
Antonino
A
Menon
Jayant
J
Walling
Jennifer
J
Bailey
Rolando
R
Rosenblum
Marc
M
Mikkelsen
Tom
T
Fine
Howard A
HA
D000818:Animals; D001921:Brain / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D015536:Down-Regulation; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000098:blood supply* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D051379:Mice; D009474:Neurons / Q000378:metabolism*; D011485:Protein Binding; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D019089:Stem Cell Factor / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D015996:Survival Rate
D034741:RNA, Small Interfering; D019089:Stem Cell Factor; C108111:fibroblast growth factor 13; D005346:Fibroblast Growth Factors; D019009:Proto-Oncogene Proteins c-kit