Adenovirus-mediated gene therapy with an antiangiogenic fragment of thrombospondin-1 inhibits human leukemia xenograft growth in nude mice
| Autor: | Bin Li, Yuling Zhou, Jacques P. Caen, Zhongchao Han, Peng Liu, Chen Yang, Gérard Tobelem, Renchi Yang, Ying-lin Cai, Shihong Lu, Yi Wang, Yanhan Li |
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| Rok vydání: | 2003 |
| Předmět: |
endocrine system
Cancer Research Angiogenesis Chronic lymphocytic leukemia Genetic enhancement Genetic Vectors Transplantation Heterologous Mice Nude Angiogenesis Inhibitors Gene delivery Biology Adenoviridae Thrombospondin 1 Mice Transduction Genetic immune system diseases medicine Animals Humans Thrombospondin Leukemia Neovascularization Pathologic virus diseases Genetic Therapy Hematology medicine.disease Peptide Fragments Treatment Outcome Oncology Immunology Cancer research Female K562 Cells Cell Division K562 cells |
| Zdroj: | Leukemia Research. 27:701-708 |
| ISSN: | 0145-2126 |
| Popis: | Recent investigations support the idea that angiogenesis is involved in the pathophysiology of leukemia. Within a given microenvironment, the angiogenic response is regulated by a delicate balance of angiogenesis inducers and inhibitors. Thrombospondin-1 (TSP-1) is a multifunctional extracellular glycoprotein showing angiostatic properties in multiple in vitro and in vivo assays. Interestingly, there is also proangiogenic domain in this complex molecule. Development of TSP-1 as an antiangiogenic drug has been hindered by multiplicity of its functional effects, difficulties in its production and its poor pharmacokinetics. The aim of the present study was to establish a recombinant adenovirus (ADV·TSP-1 f ) expressing antiangiogenic fragment of TSP-1 (TSP-1 f ), and to determine the feasibility for use of the adenovirally expressed TSP-1 f in leukemia gene therapy. The results of this investigation showed that TSP-1 f was expressed efficiently in adenovirus-transduced human myelogenous leukemia K562 cells. Compared to the controls, although there was almost no effect on proliferation of K562 cells in vitro, adenovirus-mediated TSP-1 f transduction inhibited the growth of K562 xenografts dramatically. Furthermore, the microvessel density (MVD) was much lower in the ADV·TSP-1 f -treated tumors compared to the controls. These data support the use of in vivo gene delivery approach to produce antiangiogenic fragment of TSP-1 for leukemia therapy. |
| Databáze: | OpenAIRE |
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