Journal
PHARMACEUTICALS
Volume 4, Issue 12, Pages 1551-1577Publisher
MDPI
DOI: 10.3390/ph4121551
Keywords
extracelluar matrix; endogenous angioinhibitors; tumor angiogenesis; arresten; canstatin; tumstatin; endostatin; endorepellin; angiostatin; prothrombin kringle domain 2; thrombospondin; vasohibin; PEX domain; integrin signaling
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Funding
- Flight Attendant Medical Research Institute Young Clinical Scientist Award [FAMRI-062558]
- NIH/NCI Grant [RO1CA143128]
- Dobleman Head and Neck Cancer Institute [DHNCI-61905]
- Cell Signaling, Retinal and Tumor Angiogenesis Laboratory at Boys Town National Research Hospital
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Angiogenesis, a neovascularization process induced from the existing parent blood vessels, is a prerequisite for many physiological and pathological conditions. Under physiological conditions it is regulated by a balance between endogenous angioinhibitors and angioactivators, and an imbalance between them would lead to pathological conditions such as cancer, age-related macular degeneration (AMD), diabetic retinopathy, cardiovascular diseases, etc. Several proteolytically generated endogenous molecules have been identified which exhibit angioinhibition and/or antitumor activities. These angioinhibitors interact with endothelial and tumor cells by binding to distinct integrins and initiate many of their intracellular signaling mechanisms regulating the cell survival and or apoptotic pathways. The present review will focus on the extracellular matrix derived angioinhibitors, and their mechanisms of actions that point to the clinical significance and therapeutic implications.
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