Anti-YKL-40 antibody and ionizing irradiation synergistically inhibit tumor vascularization and malignancy in glioblastoma.
Carcinogenesis
; 35(2): 373-82, 2014 Feb.
Article
em En
| MEDLINE
| ID: mdl-24282289
ABSTRACT
Chemo/radiotherapies are the most common adjuvant modality treated for patients with glioblastoma (GBM) following surgery. However, the overall therapeutic benefits are still uncertain, as the mortality remains high. Elevated expression of YKL-40 in GBM was correlated with increases in mural cell-associated vessel coverage, stability and density, and decreases in vessel permeability and disease survival. To explore the potential role of YKL-40 in mural cell-mediated tumor vascularization, we employed an anti-YKL-40 neutralizing antibody (mAY) and ionizing irradiation (IR) in xenografted brain tumor models. Although single treatment with mAY or IR partially increased mouse survival, their combination led to dramatic inhibition in tumor growth and increases in mouse survival. mAY blocked mural cell-mediated vascular stability, integrity and angiogenesis; whereas IR merely promoted tumor cell and vascular cell apoptosis. Vascular radioresistance is at least partially attributed to expression of YKL-40 in mural cells. These divergent effects were also recapitulated in cultured systems using endothelial cells and mural cells differentiated from glioblastoma stem-like cells (GSCs). Dysfunction of intercellular contact N-cadherin was found to mediate mAY-inhibited vascularization. Collectively, the data suggest that the conjunction therapy with mAY and IR synergistically inhibit tumor vascularization and progression. The evidence may shed light on a new adjuvant therapy in clinic.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Radiação Ionizante
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Células-Tronco Neoplásicas
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Neoplasias Encefálicas
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Glioblastoma
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Adipocinas
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Lectinas
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Anticorpos Monoclonais
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Neovascularização Patológica
Limite:
Animals
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Humans
Idioma:
En
Revista:
Carcinogenesis
Ano de publicação:
2014
Tipo de documento:
Article