Crossref journal-article
Proceedings of the National Academy of Sciences
Proceedings of the National Academy of Sciences (341)
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.

Bibliography

Streit, M., Riccardi, L., Velasco, P., Brown, L. F., Hawighorst, T., Bornstein, P., & Detmar, M. (1999). Thrombospondin-2: A potent endogenous inhibitor of tumor growth and angiogenesis. Proceedings of the National Academy of Sciences, 96(26), 14888–14893.

Authors 7
  1. Michael Streit (first)
  2. Lucia Riccardi (additional)
  3. Paula Velasco (additional)
  4. Lawrence F. Brown (additional)
  5. Thomas Hawighorst (additional)
  6. Paul Bornstein (additional)
  7. Michael Detmar (additional)
References 41 Referenced 233
  1. 10.1073/pnas.88.19.8636
  2. 10.1096/fasebj.6.14.1426766
  3. 10.1016/0960-9822(93)90270-X
  4. 10.1016/S0021-9258(18)98764-8
  5. 10.1016/0076-6879(94)45006-4
  6. 10.1016/S0021-9258(19)50727-X
  7. 10.1016/S0021-9258(18)31625-9
  8. 10.1074/jbc.271.27.15993
  9. 10.1002/aja.1001970105
  10. 10.1177/002215549804600904
  11. Detmar M. (2000) J. Invest. Dermatol. Symp. Proc. in press.
  12. 10.1002/(SICI)1097-4652(199604)167:1<164::AID-JCP19>3.0.CO;2-B
  13. M Reed, L Iruela-Arispe, E O'Brien, T Truong, T LaBell, P Bornstein, E Sage Am J Pathol 147, 1068–1080 (1995). / Am J Pathol by Reed M (1995)
  14. 10.1006/bbrc.1995.2780
  15. 10.1016/S0021-9258(19)74381-6
  16. 10.1083/jcb.140.2.419
  17. 10.1007/978-1-59259-453-5_12
  18. S D Weinstat, V S Zabrenetzky, K VanHoutte, W A Frazier, D D Roberts, P S Steeg Cancer Res 54, 6504–6511 (1994). / Cancer Res by Weinstat S D (1994)
  19. 10.1073/pnas.96.5.2065
  20. 10.1016/S0002-9440(10)65140-1
  21. O Melnyk, M A Shuman, K J Kim Cancer Res 56, 921–924 (1996). / Cancer Res by Melnyk O (1996)
  22. 10.1006/excr.1998.3936
  23. 10.1084/jem.180.3.1141
  24. 10.1091/mbc.3.2.211
  25. 10.1038/227680a0
  26. W Gorczyca, J Gong, Z Darzynkiewicz Cancer Res 53, 1945–1951 (1993). / Cancer Res by Gorczyca W (1993)
  27. D R Senger, S R Ledbetter, K P Claffey, A Papadopoulos-Sergiou, C A Perruzzi, M Detmar Am J Pathol 149, 293–305 (1996). / Am J Pathol by Senger D R (1996)
  28. 10.1111/1523-1747.ep12286453
  29. 10.1172/JCI1684
  30. 10.1046/j.1523-1747.1998.00262.x
  31. 10.1096/fasebj.9.10.7615160
  32. 10.1073/pnas.96.8.4449
  33. Kyriakides T. R. Tam J. W. Y. & Bornstein P. (1999) J. Invest. Dermatol. in press.
  34. N Bertin, P Clezardin, R Kubiak, L Frappart Cancer Res 57, 396–399 (1997). / Cancer Res by Bertin N (1997)
  35. Y Oshika, K Masuda, T Tokunaga, H Hatanaka, T Kamiya, Y Abe, Y Ozeki, H Kijima, H Yamazaki, N Tamaoki, et al. Clin Cancer Res 4, 1785–1788 (1998). / Clin Cancer Res by Oshika Y (1998)
  36. 10.1038/sj.bjc.6690056
  37. L F Brown, M Detmar, K Claffey, J A Nagy, D Feng, A M Dvorak, H F Dvorak EXS 79, 233–269 (1997). / EXS by Brown L F (1997)
  38. 10.1083/jcb.122.2.497
  39. 10.1083/jcb.138.3.707
  40. 10.1126/science.284.5415.808
  41. 10.1007/978-3-642-45769-2_33
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)
Funders 0

None

@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} }