Related Experiment Video
Updated: May 6, 2026
An In Vitro System to Study Tumor Dormancy and the Switch to Metastatic Growth
Published on: August 11, 2011
Angiostatin induces and sustains dormancy of human primary tumors in mice
M S O'Reilly1, L Holmgren, C Chen
1Department of Surgery, Children's Hospital, Boston, Massachusetts, USA.
Abstract:
There is now considerable direct evidence that tumor growth is angiogenesis-dependent. The most compelling evidence is based on the discovery of angiostatin, an angiogenesis inhibitor that selectively instructs endothelium to become refractory to angiogenic stimuli. Angiostatin, which specifically inhibits endothelial proliferation, induced dormancy of metastases defined by a balance of apoptosis and proliferation. We now show that systemic administration of human angiostatin potently inhibits the growth of three human and three murine primary carcinomas in mice. An almost complete inhibition of tumor growth was observed without detectable toxicity or resistance. The human carcinomas regressed to microscopic dormant foci in which tumor cell proliferation was balanced by apoptosis in the presence of blocked angiogenesis. This regression of primary tumors without toxicity has not been previously described. This is also the first demonstration of dormancy therapy, a novel anticancer strategy in which malignant tumors are regressed by prolonged blockade of angiogenesis.
Insights
Systemic administration of human angiostatin effectively inhibited primary tumor growth in mice. This novel dormancy therapy strategy induced tumor regression without toxicity, offering a new approach to cancer treatment.
Area of Science:
- Oncology
- Cancer Biology
- Angiogenesis Research
Background:
- Tumor growth is critically dependent on angiogenesis, the formation of new blood vessels.
- Angiostatin, an endogenous inhibitor of angiogenesis, has shown potential in controlling tumor spread.
- Previous studies indicated angiostatin's role in inducing tumor dormancy by inhibiting endothelial proliferation.
Purpose of the Study:
- To evaluate the efficacy of systemic human angiostatin administration in inhibiting primary tumor growth.
- To investigate the potential of angiostatin as a novel anticancer strategy for inducing tumor dormancy.
- To assess the toxicity and resistance associated with prolonged angiostatin treatment.
Main Methods:
- Systemic administration of human angiostatin to mice bearing human and murine primary carcinomas.
- Monitoring tumor growth inhibition, regression, and the induction of tumor dormancy.
- Assessing tumor cell proliferation, apoptosis, and angiogenesis blockade.
- Evaluating for any detectable toxicity or development of resistance.
Main Results:
- Potent inhibition of primary tumor growth was observed in all tested human and murine carcinomas.
- Human carcinomas regressed to microscopic dormant foci, characterized by a balance of apoptosis and proliferation.
- Tumor regression occurred without detectable toxicity or resistance, a previously undescribed outcome.
- Angiogenesis was effectively blocked in the dormant tumor foci.
Conclusions:
- Systemic human angiostatin is a potent inhibitor of primary tumor growth and induces tumor dormancy.
- Angiostatin-mediated dormancy therapy represents a novel and non-toxic anticancer strategy.
- Blocking angiogenesis is a viable therapeutic approach for achieving sustained tumor regression and control.
