Bevacizumab potentiates chemotherapeutic effect on T-leukemia/lymphoma cells by direct action on tumor endothelial cells.
Haematologica
; 96(6): 927-31, 2011 Jun.
Article
em En
| MEDLINE
| ID: mdl-21330328
ABSTRACT
Vascular endothelial growth factor-A, an angiogenesis stimulator expressed on both tumor endothelial and malignant T cells, is involved in tumor progression in T-leukemia/lymphoma. Here, we assessed the impact of therapeutic vascular endothelial growth factor-A blockade on tumor-endothelial cell interaction and on tumor progression. In a murine xenograft T-leukemia/lymphoma model, combined bevacizumab (monoclonal antibody against vascular endothelial growth factor-A) with doxorubicin, compared with doxorubicin alone, significantly delayed tumor growth and induced prevalence of tumor cell apoptosis over mitosis. More importantly, the combined treatment induced endothelial cell swelling, microvessel occlusions, and tumor necrosis. In vitro, co-culture of endothelial cells with T-leukemia/lymphoma cells showed that doxorubicin induced expression of intracellular cell adhesion molecule-1, provided endothelial and malignant T cells were in direct contact. This was abrogated by bevacizumab treatment with doxorubicin. Taken together, bevacizumab enhances the chemotherapeutic effect on T-leukemia/lymphoma cells. Directly targeting tumor endothelial cells might be a promising therapeutic strategy to counteract tumor progression in T-cell malignancies.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Leucemia de Células T
/
Linfoma de Células T
/
Células Endoteliais
/
Fator A de Crescimento do Endotélio Vascular
/
Anticorpos Monoclonais
/
Antineoplásicos
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Haematologica
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
China