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Spotlight on Angiogenesis

Antiangiogenic treatment with endostatin inhibits progression of AML in vivo

Leukemia volume 19, pages 1312–1317 (2005)Cite this article

Abstract

Increased vessel density in the bone marrow of patients with acute myeloid leukemia as well as elevated expression of proangiogenic factors by leukemic cells implies a central role of angiogenesis in hematological malignancies. Endostatin (ES), a fragment of collagen XVIII, is an endogenous inhibitor of angiogenesis that has shown therapeutic activity in solid tumors in various preclinical models. Using microencapsulation technology, we studied the therapeutic effect of ES in AML. While ES had no effect on proliferation of M1 murine leukemic cells in vitro, ES producing microbeads significantly inhibited growth of subcutaneous chloromas in SCID mice as compared to controls. In a leukemia model using M1 cells the concomitant treatment of mice with ES microbeads prolonged median survival significantly. Histological analysis revealed a decreased microvessel density and a reduced number of CD31-positive single cells, putatively endothelial progenitor cells, in the bone marrow of treated animals. Taken together, ES has inhibitory effects on neo-angiogenesis in the bone marrow and on progression of leukemia in vivo. These experiments suggest a possible therapeutic role of antiangiogenic gene therapy with ES in AML.

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Acknowledgements

This work was in part supported by the Erich-Roggenbuck-Stiftung (GS, SE) and a BMBF grant (SL, WF). The authors are grateful to Kirsten Miethe and Katrin Kluge for their excellent technical assistance.

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Authors and Affiliations

  1. Department of Medicine, Oncology and Hematology, University Hospital Hamburg-Eppendorf, Hamburg, Germany

    G Schuch, S Loges, E Laack, C Bokemeyer, D K Hossfeld & W Fiedler

  2. Institute of Anatomy, University Hospital Hamburg-Eppendorf, Hamburg, Germany

    L Oliveira-Ferrer & S Ergun

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  1. G Schuch
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Correspondence to G Schuch.

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Schuch, G., Oliveira-Ferrer, L., Loges, S. et al. Antiangiogenic treatment with endostatin inhibits progression of AML in vivo. Leukemia 19, 1312–1317 (2005). https://doi.org/10.1038/sj.leu.2403824

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