Cited by 4,486Angiogenesis and VEGF in CancerVascular Tumors and AngiosarcomasProtease and Inhibitor Mechanisms

Endostatin: an endogenous inhibitor of angiogenesis and tumor growth

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O'Reilly, Michael S, Boehm, Thomas, Shing, Yuen, Fukai, Naomi, Vasios, George, Lane, William S, Flynn, Evelyn, Birkhead, James R +2 more·1997·Cell

Abstract

We previously identified the angiogenesis inhibitor angiostatin. Using a similar strategy, we have identified endostatin, an angiogenesis inhibitor produced by hemangioendothelioma. Endostatin is a 20 kDa C-terminal fragment of collagen XVIII. Endostatin specifically inhibits endothelial proliferation and potently inhibits angiogenesis and tumor growth. By a novel method of sustained release, E. coli-derived endostatin was administered as a nonrefolded suspension. Primary tumors were regressed to dormant microscopic lesions. Immunohistochemistry revealed blocked angiogenesis accompanied by high proliferation balanced by apoptosis in tumor cells. There was no toxicity. Together with angiostatin data, these findings validate a strategy for identifying endogenous angiogenesis inhibitors, suggest a theme of fragments of proteins as angiogenesis inhibitors, and demonstrate dormancy therapy.

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Crossref · 10.1016/s0092-8674(00)81848-6

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Authors
O'Reilly, M. S., Boehm, T., Shing, Y., Fukai, N., Vasios, G., Lane, W. S., Flynn, E., Birkhead, J. R., Olsen, B. R., & Folkman, J.
Affiliations
  • Boston Children's Hospital (US)
  • Harvard University (US)
Corresponding author
Folkman, Judah
Venue
Cell
Publisher
Elsevier BV
Published
1997-01
Volume
88
Issue
2
Pages
277-285
ISSN
0092-8674 (ISSN-L)
OpenAlex
W2131798870
Cited by
4,486
References
87
Citations by year
2026: 28 · 2025: 28 · 2024: 54 · 2023: 63 · 2022: 68 · 2021: 89 · 2020: 87 · 2019: 79 · 2018: 95 · 2017: 99 · 2016: 100 · 2015: 110 · 2014: 152 · 2013: 131 · 2012: 152
FWCI
74.68
Type
journal article
Language
en
Open access
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r01hl040711-03, 5p01hl033014-10)
  • National Heart, Lung, and Blood Institute (HL 33014, HL-40711)
  • National Cancer Institute (P01CA045548, P0-1 CA-45548)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
  • Health Sciences › Medicine › Oncology › Vascular Tumors and Angiosarcomas
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
Keywords
endostatin, angiogenesis inhibitors, angiostatin, collagen XVIII, hemangioendothelioma, tumor growth inhibition, endothelial cell proliferation, tumor dormancy, apoptosis, protein fragments, sustained drug release, tumor regression
MeSH terms
Amino Acid Sequence, Animals, Antineoplastic Agents, Capillaries, Cell Division, Collagen, Endothelium, Vascular, Hemangioendothelioma, Male, Mice, Inbred C57BL, Mice, Inbred Strains, Molecular Sequence Data, Neoplasm Metastasis, Neoplasms, Experimental, Neovascularization, Pathologic, Peptide Fragments, Recombinant Proteins, Tumor Cells, Cultured, Culture Media, Conditioned, Neovascularization, Physiologic, Endostatins, Collagen Type XVIII, Mice

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