scholarly journals The N-Terminal Domain of Thrombospondin-1: a Key for the Dual Effect of TSP-1 in Angiogenesis and Cancer Progression?

2009 ◽  
Vol 9 ◽  
pp. 133-136 ◽  
Author(s):  
Verônica Morandi
Keyword(s):  
Cancer Progression ◽  
Dual Effect ◽  
Terminal Domain ◽  
Thrombospondin 1

An Amyloid-Like C-Terminal Domain of Thrombospondin-1 Displays CD47 Agonist Activity Requiring Both VVM Motifs†

Biochemistry ◽  
2003 ◽  
Vol 42 (33) ◽  
pp. 10001-10011 ◽  
Author(s):  
J. F. McDonald ◽  
J. M. Dimitry ◽  
W. A. Frazier
Keyword(s):  
Agonist Activity ◽  
Terminal Domain ◽  
Thrombospondin 1

Syndecan-4 contributes to endothelial tubulogenesis through interactions with two motifs inside the pro-angiogenic N-terminal domain of thrombospondin-1

2007 ◽  
Vol 214 (3) ◽  
pp. 828-837 ◽  
Author(s):  
Sara Santana Nunes ◽  
Marianna A. Ferrari do Outeiro-Bernstein ◽  
Luiz Juliano ◽  
Francisco Vardiero ◽  
Helena B. Nader ◽  
...  
Keyword(s):  
Terminal Domain ◽  
Thrombospondin 1

scholarly journals The Structures of the Thrombospondin-1 N-Terminal Domain and Its Complex with a Synthetic Pentameric Heparin

Structure ◽  
2006 ◽  
Vol 14 (1) ◽  
pp. 33-42 ◽  
Author(s):  
Kemin Tan ◽  
Mark Duquette ◽  
Jin-huan Liu ◽  
Rongguang Zhang ◽  
Andrzej Joachimiak ◽  
...  
Keyword(s):  
Terminal Domain ◽  
Thrombospondin 1

scholarly journals Dual Effect of Serum Amyloid A on the Invasiveness of Glioma Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Franciele Hinterholz Knebel ◽  
Renata Chaves Albuquerque ◽  
Renato Ramos Massaro ◽  
Silvya Stuchi Maria-Engler ◽  
Ana Campa
Keyword(s):  
Tumor Progression ◽  
Tumor Cells ◽  
Cancer Progression ◽  
Serum Amyloid A ◽  
Thymidine Incorporation ◽  
Serum Amyloid ◽  
Migration And Invasion ◽  
Dual Effect ◽  
Amyloid A ◽  
Protein Serum

Evidence sustains a role for the acute-phase protein serum amyloid A (SAA) in carcinogenesis and metastasis, and the protein has been suggested as a marker for tumor progression. Nevertheless, the demonstration of a direct activity of SAA on tumor cells is still incipient. We have investigated the effect of human recombinant SAA (rSAA) on two human glioma cell lines, A172 and T98G. rSAA stimulated the [3H]-thymidine incorporation of both lines, but had dual effects on migration and invasiveness which varied according to the cell line. In T98G, the rSAA increased migration and invasion behaviors whereas in A172 it decreased these behaviors. These findings agree with the effect triggered by rSAA on matrix metalloproteinases (MMPs) activities measured in a gelatinolytic assay. rSAA inhibited activity of both MMPs in A172 cells while increasing them in T98G cells. rSAA also affected the production of compounds present in the tumor microenvironment that orchestrate tumor progression, such as IL-8, the production of reactive oxygen species (ROS) and nitric oxide (NO). We also observed that both lines expressed all three of the isoforms of SAA: SAA1, SAA2, and SAA4. These data suggest that some tumor cells are responsive to SAA and, in these cases, SAA may have a role in cancer progression that varies according to the cell type.

scholarly journals Cell-type specific adhesive interactions of skeletal myoblasts with thrombospondin-1.

1994 ◽  
Vol 5 (4) ◽  
pp. 423-437 ◽  
Author(s):  
J C Adams ◽  
J Lawler
Keyword(s):  
Skeletal Muscle ◽  
Fusion Protein ◽  
Chondroitin Sulphate ◽  
Attachment Site ◽  
Globular Domain ◽  
Terminal Domain ◽  
Carboxy Terminal Domain ◽  
Chondroitin Sulphate Proteoglycans ◽  
Thrombospondin 1 ◽  
Carboxy Terminal

Thrombospondin-1 (TSP-1) is an extracellular matrix glycoprotein that may play important roles in the morphogenesis and repair of skeletal muscle. To begin to explore the role of thrombospondin-1 in this tissue, we have examined the interactions of three rodent skeletal muscle cell lines, C2C12, G8, and H9c2, with platelet TSP-1. The cells secrete thrombospondin and incorporate it into the cell layer in a distribution distinct from that of fibronectin. Myoblasts attach and spread on fibronectin- or thrombospondin-coated substrates with similar time and concentration dependencies. Whereas cells adherent on fibronectin organize actin stress fibers, cells adherent on TSP-1 display prominent membrane ruffles and lamellae that contain radial actin microspikes. Attachment to thrombospondin-1 or the 140-kDa tryptic fragment is mediated by interactions with the type 1 repeats and the carboxy-terminal globular domain. Attachment is not inhibited by heparin, GRGDSP peptide, or VTCG peptide but is inhibited by chondroitin sulphate A. Integrins of the beta 1 or alpha V subgroups do not appear to be involved in myoblast attachment to TSP-1; instead, this process depends in part on cell surface chondroitin sulphate proteoglycans. Whereas the central 70-kDa chymotryptic fragment of TSP-1 does not support myoblast attachment, the carboxy-terminal domain of TSP-1 expressed as a fusion protein in the bacterial expression vector, pGEX, supported myoblast attachment to 30% the level of intact TSP-1. Thrombospondin-4 (TSP-4) is also present in skeletal muscle and a fusion protein containing the carboxy-terminal domain of TSP-4 also supported myoblast adhesion, although this protein was less active on a molar basis than the TSP-1 fusion protein. Thus, the carboxyterminal domain of TSP-1 appears to contain a primary attachment site for myoblasts, and this activity is present in a second member of the thrombospondin family.

Type 3 repeat/C-terminal domain of thrombospondin-1 triggers caspase-independent cell death through CD47/αvβ3 in promyelocytic leukemia NB4 cells

Blood ◽  
2005 ◽  
Vol 106 (2) ◽  
pp. 658-667 ◽  
Author(s):  
Anne Saumet ◽  
Mouna Ben Slimane ◽  
Michel Lanotte ◽  
Jack Lawler ◽  
Véronique Dubernard
Keyword(s):  
Cell Death ◽  
Solid Tumors ◽  
Promyelocytic Leukemia ◽  
Leukemia Cell Line ◽  
Death Process ◽  
Antitumor Action ◽  
Terminal Domain ◽  
Apoptosis Protein ◽  
Thrombospondin 1 ◽  
Type 3

Abstract By means of its antiangiogenic activity, thrombospondin-1 (TSP-1) exerts indirect antitumoral action on solid tumors. Here, we investigated potential antitumor action in an in vitro cell model for promyelocytic leukemia (NB4-LR1), resistant to retinoid maturation. Purified soluble TSP-1 added to cultures induced a strong dose-dependent growth inhibition and a slowly developing maturation-independent cell death. Recombinant fragments of TSP-1 allowed mapping of these activities to its type 3 repeat/C-terminal domain, features that are distinct from those of TSP-1 action on solid tumors, previously ascribed to the type 1 repeat domain. Cell death in leukemia was characterized as a caspase-independent mechanism, without DNA fragmentation, but phosphatidylserine externalization followed by membrane permeabilization. Mitochondria membrane depolarization was inherent to TSP-1 action but did not produce release of death-promoting proteins (eg, noncaspase apoptosis regulators, apoptosis-induced factor [AIF], endonuclease G, or Omi/HtrA2 or the caspase regulators, cytochrome c or second mitochondrial activator of caspase/direct inhibitor of apoptosis protein-binding protein with low isoelectric point [Smac/DIABLO]). Although detected, reactive oxygen species (ROS) production was likely not involved in the death process. Finally, receptor agonist RFYVVM and RGD peptides indicated that TSP-1 death effects are mediated by membrane receptors CD47 and αvβ3. These results demonstrated a new domain-specific antitumoral activity of TSP-1 on a leukemia cell line, which extends TSP-1 therapeutic potential outside the area of vascularized solid tumors. (Blood. 2005;106:658-667)

scholarly journals Thrombospondin-1-N-Terminal Domain Induces a Phagocytic State and Thrombospondin-1-C-Terminal Domain Induces a Tolerizing Phenotype in Dendritic Cells

PLoS ONE ◽  
2009 ◽  
Vol 4 (8) ◽  
pp. e6840 ◽  
Author(s):  
Adi Tabib ◽  
Alon Krispin ◽  
Uriel Trahtemberg ◽  
Inna Verbovetski ◽  
Mario Lebendiker ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Terminal Domain ◽  
Thrombospondin 1
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