Abstract
The phenomenon of inhibition of tumor growth by tumor mass has been repeatedly studied, but without elucidation of a satisfactory mechanism. In our animal model, a primary tumor inhibits its remote metastases. After tumor removal, metastases neovascularize and grow. When the primary tumor is present, metastatic growth is suppressed by a circulating angiogenesis inhibitor. Serum and urine from tumor-bearing mice, but not from controls, specifically inhibit endothelial cell proliferation. The activity copurifies with a 38 kDa plasminogen fragment that we have sequenced and named angiostatin. A corresponding fragment of human plasminogen has similar activity. Systemic administration of angiostatin, but not intact plasminogen, potently blocks neovascularization and growth of metastases. We here show that the inhibition of metastases by a primary mouse tumor is mediated, at least in part, by angiostatin.
Keywords
AngiostatinLewis lung carcinomaBiologyAngiogenesisCancer researchNeovascularizationAngiogenesis inhibitorPrimary tumorMetastasisEndostatinLung cancerLungCancerPathologyInternal medicineMedicine
MeSH Terms
Amino Acid SequenceAngiostatinsAnimalsCarcinomaLewis LungCattleEndotheliumVascularGrowth InhibitorsIn Vitro TechniquesMaleMiceMiceInbred C57BLMolecular Sequence DataNeoplasm MetastasisNeovascularizationPathologicPeptide FragmentsPlasminogen
Affiliated Institutions
Related Publications
Angiogenesis in cancer, vascular, rheumatoid and other disease
Recent discoveries of endogenous negative regulators of angiogenesis, thrombospondin, angiostatin and glioma-derived angiogenesis inhibitory factor, all associated with neovascu...
Inhibition of vascular endothelial growth factor reduces angiogenesis and modulates immune cell infiltration of orthotopic breast cancer xenografts
Abstract Vascular endothelial growth factor (VEGF) is a primary stimulant of angiogenesis and is a macrophage chemotactic protein. Inhibition of VEGF is beneficial in combinatio...
An Orally Available Small-Molecule Inhibitor of c-Met, PF-2341066, Exhibits Cytoreductive Antitumor Efficacy through Antiproliferative and Antiangiogenic Mechanisms
Abstract The c-Met receptor tyrosine kinase and its ligand, hepatocyte growth factor (HGF), have been implicated in the progression of several human cancers and are attractive t...
Cure of Xenografted Human Carcinomas by BR96-Doxorubicin Immunoconjugates
Immunoconjugates (BR96-DOX) were prepared between chimeric monoclonal antibody BR96 and the anticancer drug doxorubicin. The monoclonal antibody binds an antigen related to Lewi...
Immune-Mediated Inhibition of Metastases after Treatment with Local Radiation and CTLA-4 Blockade in a Mouse Model of Breast Cancer
Abstract Purpose: Ionizing radiation therapy (RT) is an important component in the management of breast cancer. Although the primary tumor can be successfully treated by surgery...
Publication Info
- Year
- 1994
- Type
- article
- Volume
- 79
- Issue
- 2
- Pages
- 315-328
- Citations
- 3335
- Access
- Closed
External Links
Social Impact
Altmetric
PlumX Metrics
Social media, news, blog, policy document mentions
Citation Metrics
3335
OpenAlex
62
Influential
2540
CrossRef
Cite This
M. OʼReilly
(1994).
Angiostatin: A novel angiogenesis inhibitor that mediates the suppression of metastases by a lewis lung carcinoma.
Cell
, 79
(2)
, 315-328.
https://doi.org/10.1016/0092-8674(94)90200-3
Identifiers
- DOI
- 10.1016/0092-8674(94)90200-3
- PMID
- 7525077