What produces thrombospondin?
TSP-1 was found in vitreous of normal rat and man. TSP-1 is a 450-kDa multifunctional ECM glycoprotein produced by endothelial cells, monocytes/macrophages, smooth muscle cells, platelets, and RPE cells.
Where is thrombospondin found?
Thrombospondins. Thrombospondins are a family of multifunctional proteins. Thrombospondin-1 was first identified as the most abundant protein in platelet α granules, but is found in many tissues during development, including bone (Robey et al., 1989).
How does thrombospondin inhibit angiogenesis?
Thrombospondins TSP-1 and TSP-2 are potent endogenous inhibitors of angiogenesis. They inhibit angiogenesis through direct effects on endothelial cell migration, proliferation, survival, and apoptosis and by antagonizing the activity of VEGF.
Is thrombospondin a protein?
Thrombospondin-1 (TSP1) is a matricellular protein that is transiently expressed in extracellular matrix and modulates cell function in a context-specific manner by engaging cell surface receptors and other components of the extracellular matrix (Bornstein, 1995; Roberts and Lau, 2011).
What is thrombospondin function?
Thrombospondin (TSP), the major alpha-granule protein of human platelets, binds to the activated platelet surface upon platelet stimulation. TSP has hemagglutinating (lectin-like) activity and forms a specific complex with fibrinogen.
What do Thrombospondins do?
The thrombospondins are a multifunctional family of glycoproteins which regulates migration, cellular attachment, and invasion. They are secreted in the extracellular matrix where they interact with other growth factors and signaling molecules to influence antiangiogenic and antiproliferative effects.
What is the drug endostatin?
A recombinant human proteolytic fragment of the C-terminal end of type XVIII collagen. Endostatin induces microvascular endothelial cell apoptosis and inhibits endothelial proliferation and angiogenesis, which may result in a reduction in tumor burden.
Does endostatin cause apoptosis?
Endostatin is a well-characterized inhibitor of angiogenesis that causes apoptosis (Nguyen et al., 2009) and has been found to induce autophagy in ECs (Chau et al., 2003) and enhance BECLIN-1 expression through β-catenin and Wnt-mediated signaling pathways (Gao et al., 2010).
How does VEGF stimulate angiogenesis?
VEGF promotes tumor angiogenesis through several mechanisms, including enhanced endothelial cell proliferation and survival; increased migration and invasion of endothelial cells; increased permeability of existing vessels, forming a lattice network for endothelial cell migration; and enhanced chemotaxis and homing of …
Is endostatin still used?
Possible cancer treatment Endostatin is currently being studied as part of cancer research. Prior results indicated that endostatin can be beneficial in combinations with other medicines, but endostatin alone gave no significant improvements in tumor/disease progression.
What is the structure of fibronectin?
Structure. Fibronectin exists as a protein dimer, consisting of two nearly identical polypeptide chains linked by a pair of C-terminal disulfide bonds. Each fibronectin subunit has a molecular weight of ~230–~275 kDa and contains three types of modules: type I, II, and III.
Is endostatin FDA approved?
Endostatin has been approved by the US Food and Drug Administration (FDA) for the treatment of NV-related cancer; thus, it may be an additional drug that can be added to anti-VEGF therapy to treat corneal NV- and lymphangiogenesis-related disorders.
What are thrombospondins?
Thrombospondins are a family of secreted glycoproteins with antiangiogenic functions. Due to their dynamic role within the extracellular matrix they are considered matricellular proteins. The first member of the family, thrombospondin 1 (THBS1), was discovered in 1971 by Nancy L. Baenziger.
What are thrombospondins (TSPS) and what are their antiangiogenic properties?
Thrombospondins (TSPs) are 450-kDa trimeric glycoproteins associated with stabilization of platelets during blood clotting. Good et al. [ 50] demonstrated antiangiogenic properties of TSP-1. TSP-2 [ 129 ], as well as fragments of TSP-1 [ 124 ], also have been shown to inhibit angiogenesis.
How many subunits are in the thrombospondin family?
The family consists of thrombospondins 1-5 and can be divided into 2 subgroups: A, which contains TSP-1 and TSP-2, and B, which contains TSP-3, TSP-4 and TSP-5 (also designated cartilage oligomeric protein or COMP). TSP-1 and TSP-2 are homotrimers, consisting of three identical subunits, whereas TSP-3, TSP-4 and TSP-5 are homopentamers.
Who discovered Thrombospondin 1?
The first member of the family, thrombospondin 1 (THBS1), was discovered in 1971 by Nancy L. Baenziger. The thrombospondins are a family of multifunctional proteins.