Journal
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
Volume 1765, Issue 2, Pages 178-188Publisher
ELSEVIER
DOI: 10.1016/j.bbcan.2005.11.002
Keywords
thrombospondin-1; angiogenesis; tumor progression; metastasis; gene; TGF-beta
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Funding
- NCI NIH HHS [CA92644] Funding Source: Medline
- NHLBI NIH HHS [R01 HL080192, HL68033] Funding Source: Medline
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Angiogenesis plays a critical role in the growth and metastasis of tumors. Thrombospondin-1 (TSP-1) is a potent angiogenesis inhibitor, and down-regulation of TSP-1 has been suggested to alter tumor growth by modulating angiogenesis in a variety of tumor types. Expression of TSP-1 is up-regulated by the tumor suppressor gene, p53, and down-regulated by oncogenes such as Myc and Ras. TSP-1 inhibits angiogenesis by inhibiting endothelial cell migration and proliferation and by inducing apoptosis. In addition, activation of transforming growth factor beta (TGF-beta) by TSP-1 plays a crucial role in the regulation of tumor progression. An understanding of the molecular basis of TSP-1-mediated inhibition of angiogenesis and tumor progression will aid in the development of novel therapeutics for the treatment of cancer. (c) 2005 Elsevier B.V. All rights reserved.
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