DOI: 10.1073/pnas.95.11.6367. Angiostatin gene transfer: Inhibition of tumor growth <i>in vivo</i> by blockage of endothelial cell proliferation associated with a mitosis arrest

Angiostatin gene transfer: Inhibition of tumor growth in vivo by blockage of endothelial cell proliferation associated with a mitosis arrest

10.1073/pnas.95.11.6367

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

The antitumoral effects that follow the local delivery of the N-terminal fragment of human plasminogen (angiostatin K3) have been studied in two xenograft murine models. Angiostatin delivery was achieved by a defective adenovirus expressing a secretable angiostatin K3 molecule from the cytomegalovirus promoter (AdK3). In in vitro studies, AdK3 selectively inhibited endothelial cell proliferation and disrupted the G 2 /M transition induced by M-phase-promoting factors. AdK3-infected endothelial cells showed a marked mitosis arrest that correlated with the down-regulation of the M-phase phosphoproteins. A single intratumoral injection of AdK3 into preestablished rat C6 glioma or human MDA-MB-231 breast carcinoma grown in athymic mice was followed by a significant arrest of tumor growth, which was associated with a suppression of neovascularization within and at the vicinity of the tumors. AdK3 therapy also induced a 10-fold increase in apoptotic tumor cells as compared with a control adenovirus. Furthermore, we showed that systemic injection of AdK3 delayed C6 tumor establishment and growth, confirming that angiostatin can function in a paracrin manner. Our data support the concept that targeted antiangiogenesis, using adenovirus-mediated gene transfer, represents a promising alternative strategy for delivering antiangiogenic factors as their bolus injections present unsolved pharmacological problems.

Bibliography

Griscelli, F., Li, H., Bennaceur-Griscelli, A., Soria, J., Opolon, P., Soria, C., Perricaudet, M., Yeh, P., & Lu, H. (1998). Angiostatin gene transfer: Inhibition of tumor growth in vivo by blockage of endothelial cell proliferation associated with a mitosis arrest. Proceedings of the National Academy of Sciences, 95(11), 6367â6372.

Authors 9

Frank Griscelli (first)
Hong Li (additional)
Annelise Bennaceur-Griscelli (additional)
Jeannette Soria (additional)
Paule Opolon (additional)
Claudine Soria (additional)
Michel Perricaudet (additional)
Patrice Yeh (additional)
He Lu (additional)

References 28 Referenced 195

10.1093/jnci/82.1.4
10.1038/nm0195-27
10.1016/S0092-8674(00)80108-7
A Hori Cancer Res 51, 6180–6184 (1991). / Cancer Res by Hori A (1991)
10.1038/362841a0
10.1016/0092-8674(94)90200-3
10.1016/S0092-8674(00)81848-6
10.1210/endo.133.3.7689950
10.1073/pnas.92.17.7799
10.1016/S0092-8674(00)81926-1
10.1038/nm0696-689
10.1074/jbc.271.46.29461
10.1093/jnci/89.1.21
10.1172/JCI115902
10.1002/(SICI)1097-0215(19960529)66:5<664::AID-IJC14>3.0.CO;2-4
10.1016/S0268-9499(97)80060-4
10.1002/jcp.1041460122
10.1182/blood.V74.3.1025.1025
A Skladanowski, A K Larsen Cancer Res 57, 818–823 (1997). / Cancer Res by Skladanowski A (1997)
B K Lee Sim, M S O’Reilly, H Liang, A H Fortier, W He, J W Madsen, R Lapcevich, C A Nacy Cancer Res 57, 1329–1334 (1997). / Cancer Res by Lee Sim B K (1997)
10.1016/S0021-9258(19)86764-9
10.1056/NEJM199101033240101
10.1096/fasebj.11.8.9240963
10.1073/pnas.80.10.2926
10.1016/0092-8674(94)90542-8
10.1038/359845a0
10.1038/bjc.1992.269
10.1038/379088a0

Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:40 a.m.)
Deposited	3 years, 4 months ago (April 13, 2022, 3:49 p.m.)
Indexed	1 month ago (July 30, 2025, 9:58 a.m.)
Issued	27 years, 3 months ago (May 26, 1998)
Published	27 years, 3 months ago (May 26, 1998)
Published Online	27 years, 3 months ago (May 26, 1998)
Published Print	27 years, 3 months ago (May 26, 1998)

Funders 0

None

BibTeX

@article{Griscelli_1998, title={Angiostatin gene transfer: Inhibition of tumor growth in vivo by blockage of endothelial cell proliferation associated with a mitosis arrest}, volume={95}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.95.11.6367}, DOI={10.1073/pnas.95.11.6367}, number={11}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Griscelli, Frank and Li, Hong and Bennaceur-Griscelli, Annelise and Soria, Jeannette and Opolon, Paule and Soria, Claudine and Perricaudet, Michel and Yeh, Patrice and Lu, He}, year={1998}, month=may, pages={6367–6372} }

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