Bevacizumab potentiates chemotherapeutic effect on T-leukemia/lymphoma cells by direct action on tumor endothelial cells

• Published in: Haematologica (Roma) Vol. 96; no. 6; pp. 927 - 931
• Main Authors: Wang, Li, Shi, Wen-Yu, Yang, Fan, Tang, Wei, Gapihan, Guillaume, Varna, Mariana, Shen, Zhi-Xiang, Chen, Sai-Juan, Leboeuf, Christophe, Janin, Anne, Zhao, Wei-Li
• Format: Journal Article
• Language: English
• Published: Pavia Ferrata Storti Foundation 01.06.2011
• Subjects: Angiogenesis Inhibitors; Angiogenesis Inhibitors - pharmacology; Animals; Antibodies, Monoclonal; Antibodies, Monoclonal - pharmacology; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; Bevacizumab; Biological and medical sciences; Brief Reports; Cancer; Cell Line, Tumor; Down-Regulation; Down-Regulation - drug effects; Endothelial Cells; Endothelial Cells - drug effects; Endothelial Cells - pathology; Hematologic and hematopoietic diseases; Humans; Intercellular Adhesion Molecule-1; Intercellular Adhesion Molecule-1 - metabolism; Jurkat Cells; Leukemia, T-Cell; Leukemia, T-Cell - pathology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Life Sciences; Lymphoma, T-Cell; Lymphoma, T-Cell - metabolism; Lymphoma, T-Cell - pathology; Medical sciences; Mice; Mice, Nude; Neovascularization, Pathologic; Neovascularization, Pathologic - pathology; Tumor Burden; Tumor Burden - drug effects; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor A - antagonists & inhibitors; Xenograft Model Antitumor Assays; Antineoplastic agent; Endothelial cell; Hematology; T lymphoma; Leukemia; Malignant hemopathy; Monoclonal antibody; Bevacizumab; Chemotherapy; Treatment; Vascular endothelium growth factor; and endothelial cells; T-cell leukemia/lymphoma; Antiangiogenic agent; Tumor cell; Cancer; bevacizumab; endothelial cells
• ISSN: 0390-6078; 1592-8721
• DOI: 10.3324/haematol.2010.037689

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.