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Updated: Aug 8, 2026

Monitoring Functionality and Morphology of Vasculature Recruited by Factors Secreted by Fast-growing Tumor-generating Cells
Published on: November 23, 2014
Thrombospondin-2: a potent endogenous inhibitor of tumor growth and angiogenesis
M Streit1, L Riccardi, P Velasco
1Cutaneous Biology Research Center and Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
Abstract:
Recent evidence suggests a potential role for thrombospondin-2 (TSP-2), a matricellular glycoprotein, in the regulation of primary angiogenesis. To directly examine the biological effect of TSP-2 expression on tumor growth and angiogenesis, human A431 squamous cell carcinoma cells, which do not express TSP-2, were stably transfected with a murine TSP-2 expression vector or with vector alone. A431 cells expressing TSP-2 did not show an altered growth rate, colony-forming ability, or susceptibility to induction of apoptosis in vitro. However, injection of TSP-2-transfected clones into the dermis of nude mice resulted in pronounced inhibition of tumor growth that was significantly stronger than the inhibition observed in A431 clones stably transfected with a thrombospondin-1 (TSP-1) expression vector, and combined overexpression of TSP-1 and TSP-2 completely prevented tumor formation. Extensive areas of necrosis were observed in TSP-2-expressing tumors, and both the density and the size of tumor vessels were significantly reduced, although tumor cell expression of the major tumor angiogenesis factor, vascular endothelial growth factor, was maintained at high levels. These findings establish TSP-2 as a potent endogenous inhibitor of tumor growth and angiogenesis.
Insights
Thrombospondin-2 (TSP-2) significantly inhibits tumor growth and angiogenesis. Overexpression of TSP-2 in cancer cells reduced tumor size and blood vessel formation, offering potential therapeutic strategies.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Thrombospondin-2 (TSP-2) is a matricellular glycoprotein implicated in regulating primary angiogenesis.
- Understanding TSP-2's role in tumor development is crucial for developing novel cancer therapies.
Purpose of the Study:
- To investigate the direct biological effects of TSP-2 expression on tumor growth and angiogenesis.
- To compare the anti-tumorigenic effects of TSP-2 with TSP-1.
Main Methods:
- Human A431 squamous cell carcinoma cells, lacking TSP-2, were stably transfected with TSP-2 or control vectors.
- Tumorigenicity and angiogenesis were assessed following subcutaneous injection into nude mice.
- In vitro assays evaluated cell growth, colony formation, and apoptosis susceptibility.
Main Results:
- TSP-2 expression did not alter in vitro cancer cell growth, colony formation, or apoptosis.
- Subcutaneous tumors formed by TSP-2-expressing cells showed significantly inhibited growth compared to controls.
- TSP-2 demonstrated stronger inhibition of tumor growth and angiogenesis than TSP-1.
- Combined TSP-1 and TSP-2 overexpression completely prevented tumor formation.
- TSP-2-expressing tumors exhibited extensive necrosis and reduced vascularization, despite maintained vascular endothelial growth factor levels.
Conclusions:
- TSP-2 acts as a potent endogenous inhibitor of tumor growth and angiogenesis.
- TSP-2's anti-angiogenic properties are significant and potentially synergistic with TSP-1.
- Targeting TSP-2 may represent a viable therapeutic strategy for inhibiting tumor progression.
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