TY - JOUR
T1 - NG2 proteoglycan promotes angiogenesis-dependent tumor growth in CNS by sequestering angiostatin.
AU - Chekenya, Martha
AU - Hjelstuen, Mari
AU - Enger, Per Øyvind
AU - Thorsen, Frits
AU - Jacob, Anne L.
AU - Probst, Beatrice
AU - Haraldseth, Olav
AU - Pilkington, Geoffrey
AU - Butt, Arthur
AU - Levine, Joel M.
AU - Bjerkvig, Rolf
PY - 2002/4
Y1 - 2002/4
N2 - During embryogenesis, the NG2 proteoglycan is expressed on immature capillary vessels, but as the vessels mature they lose this expression. NG2 is up-regulated in high-grade gliomas, but it is not clear to what extent it contributes to malignant progression. Using a combination of high spatial and temporal resolution functional magnetic resonance imaging and histopathological analyses, we show here that overexpression of NG2 increases tumor initiation and growth rates, neovascularization, and cellular proliferation, which predisposes to a poorer survival outcome. By confocal microscopy and cDNA gene array expression profiles, we also show that NG2 tumors express lower levels of hypoxia inducible factor-1a, vascular endothelial growth factor, and endogenous angiostatin in vivo compared with wild-type tumors. Moreover, we demonstrate that NG2-positive cells bind, internalize, and coimmunoprecipitate with angiostatin. These results indicate a unique role for NG2 in regulating the transition from small, poorly vascularized tumors to large, highly vascular gliomas in situ by sequestering angiostatin.
AB - During embryogenesis, the NG2 proteoglycan is expressed on immature capillary vessels, but as the vessels mature they lose this expression. NG2 is up-regulated in high-grade gliomas, but it is not clear to what extent it contributes to malignant progression. Using a combination of high spatial and temporal resolution functional magnetic resonance imaging and histopathological analyses, we show here that overexpression of NG2 increases tumor initiation and growth rates, neovascularization, and cellular proliferation, which predisposes to a poorer survival outcome. By confocal microscopy and cDNA gene array expression profiles, we also show that NG2 tumors express lower levels of hypoxia inducible factor-1a, vascular endothelial growth factor, and endogenous angiostatin in vivo compared with wild-type tumors. Moreover, we demonstrate that NG2-positive cells bind, internalize, and coimmunoprecipitate with angiostatin. These results indicate a unique role for NG2 in regulating the transition from small, poorly vascularized tumors to large, highly vascular gliomas in situ by sequestering angiostatin.
UR - http://www.scopus.com/inward/record.url?scp=0036551245&partnerID=8YFLogxK
U2 - 10.1096/fj.01-0632fje
DO - 10.1096/fj.01-0632fje
M3 - Article
C2 - 11919162
AN - SCOPUS:0036551245
SN - 0892-6638
VL - 16
SP - 586
EP - 588
JO - FASEB Journal
JF - FASEB Journal
IS - 6
ER -