Thrombospondin-2: A potent endogenous inhibitor of tumor growth and angiogenesis
Open Access
- 21 December 1999
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 96 (26), 14888-14893
- https://doi.org/10.1073/pnas.96.26.14888
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.Keywords
This publication has 41 references indexed in Scilit:
- Effects of Angiogenesis Inhibitors on Multistage Carcinogenesis in MiceScience, 1999
- A Simple Immunomagnetic Protocol for the Selective Isolation and Long-Term Culture of Human Dermal Microvascular Endothelial CellsExperimental Cell Research, 1998
- Thrombospondin-1 is required for normal murine pulmonary homeostasis and its absence causes pneumonia.JCI Insight, 1998
- Metabolism of Thrombospondin 2Journal of Biological Chemistry, 1996
- Opposite regulation of thrombospondin-1 and corticotropin-induced secreted protein/thrombospondin-2 expression by adrenocorticotropic hormone in adrenocortical cellsJournal of Cellular Physiology, 1996
- Inhibition of Angiogenesis by Thrombospondin-2Biochemical and Biophysical Research Communications, 1995
- Overexpression of vascular permeability factor/vascular endothelial growth factor and its receptors in psoriasis.The Journal of Experimental Medicine, 1994
- Differential expression of thrombospondin 1, 2, and 3 during murine developmentDevelopmental Dynamics, 1993
- The thrombospondin familyCurrent Biology, 1993
- Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4Nature, 1970