Learn More
Thrombospondin-1 (TSP-1) is a naturally occurring inhibitor of angiogenesis that is able to make normal endothelial cells unresponsive to a wide variety of inducers. Here we use both native TSP-1 and small antiangiogenic peptides derived from it to show that this inhibition is mediated by CD36, a transmembrane glycoprotein found on microvascular endothelial(More)
The activity of TGF-beta1 is regulated primarily extracellularly where the secreted latent form must be modified to expose the active molecule. Here we show that thrombospondin-1 is responsible for a significant proportion of the activation of TGF-beta1 in vivo. Histological abnormalities in young TGF-beta1 null and thrombospondin-1 null mice were(More)
In many mammalian species, the placenta is the site of synthesis of proteins in the prolactin and growth hormone family. Analysis of two such proteins, proliferin (PLF) and proliferin-related protein (PRP), revealed that they are potent regulators of angiogenesis; PLF stimulated and PRP inhibited endothelial cell migration in cell culture and(More)
An inhibitor has been identified in the conditioned medium of hamster cells and hamster-human hybrids that suppresses neovascularization in vivo in the rat cornea. Inhibitory activity was tightly linked to the presence of an active cancer suppressor gene in transformants and revertants, in segregating hybrids, and in temperature-limited transformants. It(More)
In the absence of disease, the vasculature of the mammalian eye is quiescent, in part because of the action of angiogenic inhibitors that prevent vessels from invading the cornea and vitreous. Here, an inhibitor responsible for the avascularity of these ocular compartments is identified as pigment epithelium-derived factor (PEDF), a protein previously shown(More)
As normal cells progress toward malignancy, they must switch to an angiogenic phenotype to attract the nourishing vasculature that they depend on for their growth. In cultured fibroblasts from Li-Fraumeni patients, this switch was found to coincide with loss of the wild-type allele of the p53 tumor suppressor gene and to be the result of reduced expression(More)
Thrombospondin-1 (TSP1) is a large modular matrix protein containing three identical disulfide-linked 180-kD chains that inhibits neovascularization in vivo (Good et al., 1990). To determine which of the structural motifs present in the 180-kD TSP1 polypeptide mediate the anti-angiogenic activity, a series of protease-generated fragments were tested using(More)
Interleukin (IL)-4, a crucial modulator of the immune system and an active antitumor agent, is also a potent inhibitor of angiogenesis. When incorporated at concentrations of 10 ng/ml or more into pellets implanted into the rat cornea or when delivered systemically to the mouse by intraperitoneal injection, IL-4 blocked the induction of corneal(More)
Lawrence, 1996). Although named originally for its ability to induce a transformed phenotype in cultured cells 7 its signaling pathway are frequently involved in sup-TGF-␤ also has contradictory effects on 3 Department of Pathology normal cells. Depending on the cell type and the en-Northwestern University Medical School vironment, it may stimulate or(More)
Bladder tumors are characterized by markedly increased angiogenesis when compared to the normal urothelium (NU) from which they are derived. Here, we use both cultured cells and immunohistochemistry to demonstrate a primary regulatory role for thrombospondin-1 (TSP-1), a potent inhibitor of angiogenesis, in the development of bladder tumor angiogenesis.(More)