Effects of angiostatin gene transfer on functional properties and in vivo growth of Kaposi's sarcoma cells

S. Indraccolo, M. Morini, E. Gola, F. Carrozzino, W. Habeler, S. Minghelli, L. Santi, L. Chieco-Bianchi, Y. Cao, A. Albini, D. M. Noonan

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Abstract

Gene transfer delivery of endogenous angiogenesis inhibitors such as angiostatin would circumvent problems associated with long-term administration of proteins. Kaposi's sarcoma (KS), a highly vascular neoplasm, is an excellent model for studying tumor angiogenesis and antiangiogenic agent efficacy. We investigated the effects of angiostatin gene transfer in in vitro and in vivo models of KS-induced neovascularization and tumor growth. A eukaryotic expression plasmid and a Moloney leukemia virusbased retroviral vector for expression of murine angiostatin were generated harboring the angiostatin cDNA with cleavable leader signals under the control of either the strong cytomegalovirus promoter/enhancer or the Moloney leukemia virus long terminal repeat. Angiostatin secretion was confirmed by radioimmunoprecipitation and Western blot analysis. Supernatants of angiostatin-transfected cells inhibited endothelial cell migration in vitro. Stable gene transfer of the angiostatin cDNA by retroviral vectors in KS-IMM cells resulted in sustained angiostatin expression and delayed tumor growth in nude mice, which was associated with reduced vascularization. These findings suggest that gene therapy with angiostatin might be useful for treatment of KS and possibly other highly angiogenic tumors.

Original languageEnglish
Pages (from-to)5441-5446
Number of pages6
JournalCancer Research
Volume61
Issue number14
Publication statusPublished - Jul 15 2001

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Angiostatins
Kaposi's Sarcoma
Growth
Genes
Angiogenesis Inhibitors
Neoplasms
Complementary DNA
Vascular Neoplasms
Moloney murine leukemia virus
Terminal Repeat Sequences
Cytomegalovirus
Nude Mice
Genetic Therapy
Cell Movement
Leukemia
Plasmids
Endothelial Cells
Western Blotting

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Effects of angiostatin gene transfer on functional properties and in vivo growth of Kaposi's sarcoma cells. / Indraccolo, S.; Morini, M.; Gola, E.; Carrozzino, F.; Habeler, W.; Minghelli, S.; Santi, L.; Chieco-Bianchi, L.; Cao, Y.; Albini, A.; Noonan, D. M.

In: Cancer Research, Vol. 61, No. 14, 15.07.2001, p. 5441-5446.

Research output: Contribution to journalArticle

Indraccolo, S, Morini, M, Gola, E, Carrozzino, F, Habeler, W, Minghelli, S, Santi, L, Chieco-Bianchi, L, Cao, Y, Albini, A & Noonan, DM 2001, 'Effects of angiostatin gene transfer on functional properties and in vivo growth of Kaposi's sarcoma cells', Cancer Research, vol. 61, no. 14, pp. 5441-5446.
Indraccolo S, Morini M, Gola E, Carrozzino F, Habeler W, Minghelli S et al. Effects of angiostatin gene transfer on functional properties and in vivo growth of Kaposi's sarcoma cells. Cancer Research. 2001 Jul 15;61(14):5441-5446.
Indraccolo, S. ; Morini, M. ; Gola, E. ; Carrozzino, F. ; Habeler, W. ; Minghelli, S. ; Santi, L. ; Chieco-Bianchi, L. ; Cao, Y. ; Albini, A. ; Noonan, D. M. / Effects of angiostatin gene transfer on functional properties and in vivo growth of Kaposi's sarcoma cells. In: Cancer Research. 2001 ; Vol. 61, No. 14. pp. 5441-5446.
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