Journal
PHARMACEUTICALS
Volume 3, Issue 4, Pages 1241-1278Publisher
MDPI
DOI: 10.3390/ph3041241
Keywords
angiogenesis; tumor; integrins; interactions; thrombospondin-1
Categories
Funding
- Fondazione CARIPLO
- Istituto Superiore di Sanita
- Progetto Nazionale AIDS
- Ministero dell'Istruzione, Universita e Ricerca
- Ministero della Salute
- Associazione Italiana per la Ricerca sul Cancro
- Fondazione Berlucchi
Ask authors/readers for more resources
Uncontrolled neovascularization occurs in several angiogenesis-dependent diseases, including cancer. Neovascularization is tightly controlled by the balance between angiogenic growth factors and antiangiogenic agents. The various natural angiogenesis inhibitors identified so far affect neovascularization by different mechanisms of action. Thrombospondin-1 (TSP-1) is a matricellular modular glycoprotein that acts as a powerful endogenous inhibitor of angiogenesis. It acts both indirectly, by sequestering angiogenic growth factors and effectors in the extracellular environment, and directly, by inducing an antiangiogenic program in endothelial cells following engagement of specific receptors including CD36, CD47, integrins and proteoglycans (all involved in angiogenesis). In view of its central, multifaceted role in angiogenesis, TSP-1 has served as a source of antiangiogenic tools, including TSP-1 fragments, synthetic peptides and peptidomimetics, gene therapy strategies, and agents that up-regulate TSP-1 expression. This review discusses TSP-1-based inhibitors of angiogenesis, their mechanisms of action and therapeutic potential, drawing our experience with angiogenic growth factor-interacting TSP-1 peptides, and the possibility of exploiting them to design novel antiangiogenic agents.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available