The metabolite 3-hydroxiglutaric acid effectively reduces glioblastoma growth in vivo by affecting the structural integrity of tumor vasculature.
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The metabolite 3-hydroxiglutaric acid effectively reduces glioblastoma growth in vivo by affecting the structural integrity of tumor vasculature. / Oliveira-Ferrer, Leticia; Wellbrock, Jasmin; Balabanov, Melanie; Klockow, Marianne; Hauschild, Jessica; Bokemeyer, Carsten; Fiedler, Walter; Ergun, Suleyman; Schuch, Gunter.
in: CANCER LETT, Jahrgang 326, Nr. 2, 2, 2012, S. 161-167.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - The metabolite 3-hydroxiglutaric acid effectively reduces glioblastoma growth in vivo by affecting the structural integrity of tumor vasculature.
AU - Oliveira-Ferrer, Leticia
AU - Wellbrock, Jasmin
AU - Balabanov, Melanie
AU - Klockow, Marianne
AU - Hauschild, Jessica
AU - Bokemeyer, Carsten
AU - Fiedler, Walter
AU - Ergun, Suleyman
AU - Schuch, Gunter
PY - 2012
Y1 - 2012
N2 - 3-Hydroxiglutaric acid (3-OH-GA) is a disease-specific metabolite that accumulates in tissues and body fluids of patients with Glutaric aciduria type I (GAI) and has been associated with vascular abnormalities in these kindreds. Here, we demonstrate that 3-OH-GA also affects the integrity of tumor vessels leading to tumor growth inhibition in a subcutaneous model of human glioblastoma multiforme (GBM). This effect correlated with a marked decrease of VE-Cadherin expression in endothelium of 3-OH-GA-treated tumors. Furthermore, in vitro observations indicated also a direct effect of 3-OH-GA in glioma cells that showed defective mitosis and significant proliferation inhibition. In summary, the GAI-specific metabolite 3-OH-GA significantly inhibited growth of GBM xenografts by affecting the structural integrity of tumor blood vessels and in addition by causing defective mitosis and proliferation inhibition of tumor cells.
AB - 3-Hydroxiglutaric acid (3-OH-GA) is a disease-specific metabolite that accumulates in tissues and body fluids of patients with Glutaric aciduria type I (GAI) and has been associated with vascular abnormalities in these kindreds. Here, we demonstrate that 3-OH-GA also affects the integrity of tumor vessels leading to tumor growth inhibition in a subcutaneous model of human glioblastoma multiforme (GBM). This effect correlated with a marked decrease of VE-Cadherin expression in endothelium of 3-OH-GA-treated tumors. Furthermore, in vitro observations indicated also a direct effect of 3-OH-GA in glioma cells that showed defective mitosis and significant proliferation inhibition. In summary, the GAI-specific metabolite 3-OH-GA significantly inhibited growth of GBM xenografts by affecting the structural integrity of tumor blood vessels and in addition by causing defective mitosis and proliferation inhibition of tumor cells.
KW - Animals
KW - Humans
KW - Immunohistochemistry
KW - Mice
KW - Cell Line, Tumor
KW - Oligonucleotide Array Sequence Analysis
KW - Mice, Nude
KW - Neovascularization, Pathologic
KW - Blood Vessels/drug effects
KW - Cell Division/drug effects
KW - DNA, Complementary
KW - Glioblastoma/blood supply/pathology
KW - Glutarates/pharmacology
KW - Animals
KW - Humans
KW - Immunohistochemistry
KW - Mice
KW - Cell Line, Tumor
KW - Oligonucleotide Array Sequence Analysis
KW - Mice, Nude
KW - Neovascularization, Pathologic
KW - Blood Vessels/drug effects
KW - Cell Division/drug effects
KW - DNA, Complementary
KW - Glioblastoma/blood supply/pathology
KW - Glutarates/pharmacology
M3 - SCORING: Journal article
VL - 326
SP - 161
EP - 167
JO - CANCER LETT
JF - CANCER LETT
SN - 0304-3835
IS - 2
M1 - 2
ER -
