Differential effects of angiostatin, endostatin and interferon-α1 gene transfer on in vivo growth of human breast cancer cells View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2002-06-18

AUTHORS

S Indraccolo, E Gola, A Rosato, S Minuzzo, W Habeler, V Tisato, V Roni, G Esposito, M Morini, A Albini, DM Noonan, M Ferrantini, A Amadori, L Chieco-Bianchi

ABSTRACT

The administration of different angiogenesis inhibitors by gene transfer has been shown to result in inhibition of tumor growth in animal tumor models, but the potency of these genes has been only partially evaluated in comparative studies to date. To identify the most effective anti-angiogenic molecule for delivery by retroviral vectors, we investigated the effects of angiostatin, endostatin and interferon(IFN)-α1 gene transfer in in vivo models of breast cancer induced neovascularization and tumor growth. Moloney leukemia virus-based retroviral vectors for expression of murine angiostatin, endostatin and IFN-α1 were generated, characterized, and used to transduce human breast cancer cell lines (MCF7 and MDA-MB435). Secretion of the recombinant proteins was confirmed by biological and Western blotting assays. Their production did not impair in vitro growth of these breast cancer cells nor their viability, and did not interfere with the expression of angiogenic factors. However, primary endothelial cell proliferation and migration in vitro were inhibited by supernatants of the transduced cells containing angiostatin, endostatin, and IFN-α1. Stable gene transfer of the IFN-α1 cDNA by retroviral vectors in both MCF7 and MDA-MB435 cells resulted in a marked and long-lasting inhibition of tumor growth in nude mice that was associated with reduced vascularization. Endostatin reduced the in vivo growth of MDA-MB435, but not MCF7 cells, despite similar levels of in vivo production, and angiostatin did not impair the in vivo growth of either cell line. These findings indicate heterogeneity in the therapeutic efficacy of angiostatic molecules delivered by viral vectors and suggest that gene therapy with IFN-α1 and endostatin might be useful for treatment of breast cancer. More... »

PAGES

867-878

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.gt.3301703

DOI

http://dx.doi.org/10.1038/sj.gt.3301703

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1042169711

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/12080381


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29 schema:description The administration of different angiogenesis inhibitors by gene transfer has been shown to result in inhibition of tumor growth in animal tumor models, but the potency of these genes has been only partially evaluated in comparative studies to date. To identify the most effective anti-angiogenic molecule for delivery by retroviral vectors, we investigated the effects of angiostatin, endostatin and interferon(IFN)-α1 gene transfer in in vivo models of breast cancer induced neovascularization and tumor growth. Moloney leukemia virus-based retroviral vectors for expression of murine angiostatin, endostatin and IFN-α1 were generated, characterized, and used to transduce human breast cancer cell lines (MCF7 and MDA-MB435). Secretion of the recombinant proteins was confirmed by biological and Western blotting assays. Their production did not impair in vitro growth of these breast cancer cells nor their viability, and did not interfere with the expression of angiogenic factors. However, primary endothelial cell proliferation and migration in vitro were inhibited by supernatants of the transduced cells containing angiostatin, endostatin, and IFN-α1. Stable gene transfer of the IFN-α1 cDNA by retroviral vectors in both MCF7 and MDA-MB435 cells resulted in a marked and long-lasting inhibition of tumor growth in nude mice that was associated with reduced vascularization. Endostatin reduced the in vivo growth of MDA-MB435, but not MCF7 cells, despite similar levels of in vivo production, and angiostatin did not impair the in vivo growth of either cell line. These findings indicate heterogeneity in the therapeutic efficacy of angiostatic molecules delivered by viral vectors and suggest that gene therapy with IFN-α1 and endostatin might be useful for treatment of breast cancer.
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37 IFN-α1 cDNA
38 MCF7
39 MCF7 cells
40 MDA-MB435
41 MDA-MB435 cells
42 Moloney leukemia virus-based retroviral vectors
43 Western blotting assays
44 administration
45 angiogenesis inhibitors
46 angiogenic factors
47 angiostatic molecules
48 angiostatin
49 animal tumor models
50 anti-angiogenic molecules
51 assays
52 blotting assays
53 breast cancer
54 breast cancer cell lines
55 breast cancer cells
56 cDNA
57 cancer
58 cancer cell lines
59 cancer cells
60 cell lines
61 cell proliferation
62 cells
63 comparative study
64 date
65 delivery
66 different angiogenesis inhibitors
67 differential effects
68 effect
69 effect of angiostatin
70 effective anti-angiogenic molecule
71 efficacy
72 endostatin
73 endothelial cell proliferation
74 expression
75 factors
76 findings
77 gene therapy
78 gene transfer
79 genes
80 growth
81 heterogeneity
82 human breast cancer cell lines
83 human breast cancer cells
84 inhibition
85 inhibitors
86 interferon-α1 gene transfer
87 leukemia virus-based retroviral vectors
88 levels
89 lines
90 mice
91 migration
92 model
93 molecules
94 murine angiostatin
95 neovascularization
96 nude mice
97 potency
98 primary endothelial cell proliferation
99 production
100 proliferation
101 protein
102 recombinant proteins
103 reduced vascularization
104 retroviral vectors
105 secretion
106 similar levels
107 stable gene transfer
108 study
109 supernatant
110 therapeutic efficacy
111 therapy
112 transfer
113 treatment
114 tumor growth
115 tumor model
116 vascularization
117 vector
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119 viral vectors
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