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.
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Dates
Type | When |
---|---|
Created | 23 years, 1 month ago (July 26, 2002, 10:41 a.m.) |
Deposited | 3 years, 4 months ago (April 13, 2022, 5:20 p.m.) |
Indexed | 2 months ago (June 26, 2025, 2:24 p.m.) |
Issued | 25 years, 8 months ago (Dec. 21, 1999) |
Published | 25 years, 8 months ago (Dec. 21, 1999) |
Published Online | 25 years, 8 months ago (Dec. 21, 1999) |
Published Print | 25 years, 8 months ago (Dec. 21, 1999) |
@article{Streit_1999, title={Thrombospondin-2: A potent endogenous inhibitor of tumor growth and angiogenesis}, volume={96}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.96.26.14888}, DOI={10.1073/pnas.96.26.14888}, number={26}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Streit, Michael and Riccardi, Lucia and Velasco, Paula and Brown, Lawrence F. and Hawighorst, Thomas and Bornstein, Paul and Detmar, Michael}, year={1999}, month=dec, pages={14888–14893} }