title: Bevacizumab potentiates chemotherapeutic effect on T-leukemia/lymphoma cells by direct action on tumor endothelial cells.
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.
authors.affiliation: State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Shanghai Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui Jin Er Road, Shanghai 200025, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Wen-Yu
authors.initials: WY
authors.lastname: Shi
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.forename: Wei
authors.initials: W
authors.lastname: Tang
authors.forename: Guillaume
authors.initials: G
authors.lastname: Gapihan
authors.forename: Mariana
authors.initials: M
authors.lastname: Varna
authors.forename: Zhi-Xiang
authors.initials: ZX
authors.lastname: Shen
authors.forename: Sai-Juan
authors.initials: SJ
authors.lastname: Chen
authors.forename: Christophe
authors.initials: C
authors.lastname: Leboeuf
authors.forename: Anne
authors.initials: A
authors.lastname: Janin
authors.forename: Wei-Li
authors.initials: WL
authors.lastname: Zhao
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D000068258:Bevacizumab; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D019169:Jurkat Cells; D015458:Leukemia, T-Cell / Q000473:pathology*; D016399:Lymphoma, T-Cell / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000473:pathology; D047368:Tumor Burden / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D042461:Vascular Endothelial Growth Factor A; D018799:Intercellular Adhesion Molecule-1; D000068258:Bevacizumab