Angiogenesis, the formation of new blood vessels out of pre-existing capillaries, is essential for tumor progression. Many factors have been identified that are able to inhibit angiogenesis. Here, we report the construction of a tricistronic retroviral vector encoding two inhibitors of angiogenesis expressed in mammals: the N-terminal fragment of rat prolactin (16KrPRL) and a secreted form of human platelet factor 4 (sPF4). When transduced by this retroviral vector, a rat glioblastoma cell line loses its ability of promoting endothelial cell locomotion, the initial step of angiogenesis, and the formation of an endothelial cell tube network. In spite of this encouraging in vitro result, however, the anti-angiogenic vector cannot block glioblastoma progression in animal models. These results suggest that therapeutic strategies aiming to block tumor progression through the inhibition of tumor-associated angiogenesis, should not only provide large numbers of angiogenesis inhibitors, but also target the angiogenic factors produced by tumor cells. Moreover, the data described herein may confirm recent findings from other groups which indicate that in order to successfully counteract tumor progression, drugs inhibiting new blood vessel formation should be employed in combination with traditional anti-tumor strategies, such as chemotherapy or radiotherapy.

Ciafre', S.a., Barillari, G., BONGIORNO BORBONE, L., Wannenes, F., Izquierdo, M., Farace, M.g. (2002). A tricistronic retroviral vector expressing natural antiangiogenic factors inhibits angiogenesis in vitro, but is not able to block tumor progression in vivo. GENE THERAPY, 9(4), 297-302 [10.1038/sj.gt.3301652].

A tricistronic retroviral vector expressing natural antiangiogenic factors inhibits angiogenesis in vitro, but is not able to block tumor progression in vivo

CIAFRE', SILVIA ANNA;BARILLARI, GIOVANNI;BONGIORNO BORBONE, LUCILLA;FARACE, MARIA GIULIA
2002-02-01

Abstract

Angiogenesis, the formation of new blood vessels out of pre-existing capillaries, is essential for tumor progression. Many factors have been identified that are able to inhibit angiogenesis. Here, we report the construction of a tricistronic retroviral vector encoding two inhibitors of angiogenesis expressed in mammals: the N-terminal fragment of rat prolactin (16KrPRL) and a secreted form of human platelet factor 4 (sPF4). When transduced by this retroviral vector, a rat glioblastoma cell line loses its ability of promoting endothelial cell locomotion, the initial step of angiogenesis, and the formation of an endothelial cell tube network. In spite of this encouraging in vitro result, however, the anti-angiogenic vector cannot block glioblastoma progression in animal models. These results suggest that therapeutic strategies aiming to block tumor progression through the inhibition of tumor-associated angiogenesis, should not only provide large numbers of angiogenesis inhibitors, but also target the angiogenic factors produced by tumor cells. Moreover, the data described herein may confirm recent findings from other groups which indicate that in order to successfully counteract tumor progression, drugs inhibiting new blood vessel formation should be employed in combination with traditional anti-tumor strategies, such as chemotherapy or radiotherapy.
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore BIO/13
English
Con Impact Factor ISI
Transduction, Genetic; Gene Therapy; Rats, Wistar; Retroviridae; Rats; Brain Neoplasms; Animals; Glioblastoma; Humans; Platelet Factor 4; Disease Progression; Peptide Fragments; Tumor Cells, Cultured; Reverse Transcriptase Polymerase Chain Reaction; Angiogenesis Inhibitors; Endothelium, Vascular; Genetic Vectors; Prolactin; Neovascularization, Pathologic
Ciafre', S.a., Barillari, G., BONGIORNO BORBONE, L., Wannenes, F., Izquierdo, M., Farace, M.g. (2002). A tricistronic retroviral vector expressing natural antiangiogenic factors inhibits angiogenesis in vitro, but is not able to block tumor progression in vivo. GENE THERAPY, 9(4), 297-302 [10.1038/sj.gt.3301652].
Ciafre', Sa; Barillari, G; BONGIORNO BORBONE, L; Wannenes, F; Izquierdo, M; Farace, Mg
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/9196
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