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Blood, 1 November 2004, Vol. 104, No. 9, pp. 2893-2902. Prepublished online as a Blood First Edition Paper on July 6, 2004; DOI 10.1182/blood-2004-01-0226. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-01-0226v1 104/9/2893    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Wang, E. S. Articles by Moore, M. A. S. Search for Related Content PubMed PubMed Citation Articles by Wang, E. S. Articles by Moore, M. A. S. Related Collections Hemostasis, Thrombosis, and Vascular Biology Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Targeting autocrine and paracrine VEGF receptor pathways inhibits human lymphoma xenografts in vivo Eunice S. Wang, Julie Teruya-Feldstein, Yan Wu, Zhenping Zhu, Daniel J. Hicklin, and Malcolm A. S. Moore From the Laboratory of Developmental Hematopoiesis/Cell Biology Program, the Department of Medicine, and the Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY; and ImClone Systems, New York, NY. The role of angiogenesis in lymphoproliferative diseases is not well established. We demonstrate here that human lymphoma cells secrete vascular endothelial growth factor (VEGF) and express VEGF receptor 1 (VEGFR-1) and VEGFR-2. Proliferation of non-Hodgkin lymphoma (NHL) cells under serum-free conditions was enhanced by the addition of VEGF and was blocked by VEGFR-1– and VEGFR-2–specific antibodies. To differentiate between VEGF-mediated autocrine and paracrine effects on lymphoma growth, NOD/SCID mice engrafted with human diffuse large B-cell lymphoma (DLBCL) were treated with species-specific antibodies against human VEGFR-1 (6.12), human VEGFR-2 (IMC-1C11), murine VEGFR-1 (MF-1), or murine VEGFR-2 (DC101). Treatment with 6.12 or DC101 (targeting tumor VEGFR-1 and host VEGFR-2) reduced established DLBCL xenograft growth, whereas treatment with IMC-1C11 or MF-1 (targeting tumor VEGFR-1 and host VEGFR-1) had no effect. Decreased tumor volumes after 6.12 and DC101 treatment correlated with increased tumor apoptosis and reduced vascularization, respectively, supporting the presence of autocrine VEGFR-1– and paracrine VEGFR-2–mediated pathways in lymphomagenesis. Inhibition of paracrine VEGF interactions (DC101) in these models was equivalent to their inhibition with rituximab. Combining DC101 with therapeutic agents (rituximab, 6.12, methotrexate) consistently improved tumor responses over those of single-agent therapy. These data support the further clinical development of VEGFR-targeted approaches for the therapy of aggressive DLBCL. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: N. C. Douglas, H. Tang, R. Gomez, B. Pytowski, D. J. Hicklin, C. M. Sauer, J. Kitajewski, M. V. Sauer, and R. C. Zimmermann Vascular Endothelial Growth Factor Receptor 2 (VEGFR-2) Functions to Promote Uterine Decidual Angiogenesis during Early Pregnancy in the Mouse Endocrinology, August 1, 2009; 150(8): 3845 - 3854. [Abstract] [Full Text] [PDF] A. Delmonte, M. Ghielmini, and C. 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