"TSP-1 and SIRP-α bind CD47 IgV loop xref and TSP-1 can inhibit SIRP-α-Fc binding to CD47 expressing-Jurkat cells xref ."
"The binding of CD47 to either SIRPα or TSP1 provides two anticancer strategies."
"Given recent insights into the physiological functions of CD47, potential side effects of therapeutic CD47-antibodies such as B6H12, which inhibits both CD47-SIRP and CD47-TSP1 interactions, include altered blood pressure [ xref ], hemolytic anemia, and prothrombotic or antithrombotic activities [ xref , xref ]."
"Interestingly, both TSP-1 and SIRPα are interacting with CD47 during synaptogenesis xref , xref , xref , xref , which means that other mechanisms appear to be involved in CD47-dependent regulation of the type of nerve fiber growth investigated in the present study."
"Notably, the widely used CD47 blocking antibody B6H12 inhibits binding of both SIRPα and TSP1 to cell surface CD47 ( xref )."
"However, CD47 modified nanoparticles showed a prominent anti-phagocytosis property in M1 cells that may in part be due to the complex signalling interactions of CD47 with SIRPα and TSP-1."
"One approach to avoid these shortcomings is to identify and develop small molecule molecular probes and pretherapeutic agents that would (1) selectively target SIRPα or TSP1 interactions with CD47, (2) provide a route to optimize pharmacokinetics, reduce on-target toxicity and maximize tissue penetration, and (3) allow more flexible routes of administration."
"This data is consistent with competitive binding of TSP1 and SIRPα to a single site on CD47, steric inhibition of binding to distinct but proximal sites, or allosteric inhibition ( xref )."
"Thus, we propose that treatment of tumor-bearing animals with CD47 blocking antibodies, which are known to inhibit both SIRPα and TSP1 binding to CD47, could directly modulate adaptive as well as innate anti-tumor immunity."
"Indeed, CD47 antibody targeting may affect NO pathway modulation and subsequent angiogenesis regulation, since a commonly used CD47-blocking antibody (clone B6H12) was previously shown to concomitantly disrupt both TSP-1:CD47 and CD47:SIRPα interactions ( xref )."
"The COOH-terminal domain of TSP-1 binds to CD47, also known as integrin-associated protein [ xref ]."
"The COOH-terminal domain of TSP-1 binds to CD47, also known as integrin-associated protein. [ xref ] This domain also interacts with integrins such as β 1 and β v6 integrins and actively binds to proteoglycans allowing cell adhesion and spreading [ xref ]."
"To date we have validated TSP1 antibodies that block TSP1 binding to CD47, CD47 antibodies that block TSP1 binding, and antisense approaches that suppress CD47 expression [ xref , xref – xref ]."
"Previous work XREF_BIBR has shown that TNF-alpha up-regulates the TSP1, CD36, and CD47 complex in cultured myoblasts and that the TSP1-CD36-CD47 was up-regulated in sIBM."
"Finally, results show that TSP-1 utilizes cell surface receptors CD36 and CD47 to augment chemotaxis, but DBP does not bind to TSP-1, CD36 or CD47."
"Furthermore, this paper also reveals that DBP does not bind to TSP-1, CD36 or CD47 ( xref ) and that TSP-1 utilizes these cell surface receptors to augment chemotaxis to C5a ( xref – xref )."
"Ligation of CD47 by extracellular thrombospondin-1 is associated with down-regulation of IL-12 production by antigen-presenting cells [ xref ], and inhibits human naive T cell differentiation to Th1 cells but not to Th2 cells [ xref ]."
"TSP1 can also interact with integrin-bound fibrinogen, which may further increase clustering between IAP and αIIb/β3."
"This anti-angiogenic activity results in part from the ability of physiological concentrations of TSP1 binding to CD47 to control NO signaling, which is necessary for signaling by several pro angiogenic factors [XREF_BIBR]."
"Otherwise, TSP-1 binding to CD47 also inhibits differentiation of naïve T cells into Th1 ( xref ), whereas Tregs formation is induced by promoting Foxp3 transcription factor expression ( xref ; xref )."
"We have previously identified TAX2 peptide as an orthosteric antagonist for thrombospondin-1 (TSP-1) interaction with the cell-surface receptor CD47."
"56 It would be interesting to investigate the effect of CD47 blockade on the antitumour capabilities of T cells, as previous studies have suggested that CD47 negatively regulates the differentiation of Th1 CD4 + T cells 195 and interacts with TSP-1 to inhibit T cell proliferation."
"For example, B6H12 inhibits binding of TSP1 to human CD47, and TSP1 binding to CD47 inhibits NO signaling in vascular endothelial cells."
"Thus, we sought to identify an innovative selective antagonist for TSP-1:CD47 interaction."
"TSP1 binding to CD47 has global functional consequences by inhibiting endothelial nitric oxide (NO) production, controlling vascular tone, and maintaining systemic hemodynamics and cardiac dynamics in stressful conditions [ xref , xref , xref , xref ]."
"The rule for TSP1 binding to CD47 is illustrated in Figure XREF_FIG."
"The binding of CD47 to either SIRPalpha or TSP1 provides two anticancer strategies."
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"The increase in capillarity may be associated by changes in the interaction between VEGF-A, TSP-1, and CD47."
"Additional studies are required to investigate the signaling mechanism of (−)-epicatechin on the VEGF-A-TSP-1-CD47 interaction as well as determine the prolonged effects upon cessation."
"TSP-1 binds CD47 to inhibit the release of interleukin (IL)-2 ."
"TSP-1 and its potential membrane receptors, e.g. alphaIIbbeta3 integrin, CD36 and CD47, concomitantly associated with the actin cytoskeleton."
"These activities are mediated, at least in part, by interactions of TSP1 with CD47 and HSPGs on T cells (this study; xref )."
"We discussed herein the interactions of TSP-1 with well-known partners such as CD36, CD47, NO, and TGF β 1."
"Conversely, the Ca1 domain does not interact with the TSP-1 receptors CD36 and CD47, excluding their involvement in the potentiation of PDGF."
"The C-terminal domain of TSP1 binds the cell surface receptors CD36 (glycoprotein IV) and CD47 (Integrin Associated Protein, IAP, or Rh-related antigen), and both receptors have anti-angiogenic effects."
"Nevertheless, some putative side-effects of using TAX2 as an anti-cancer agent still need to be explored, particularly as TSP-1 interaction with CD47 and/or CD36 is also known to modulate platelet aggregation ( xref )."
"In endothelial cells, TSP-1 can bind to CD36 and CD47 through its type-1 repeats and carboxyl-terminal domain to inhibit cell proliferation and promote anti-angiogenic events xref , xref ."
"Through its original mechanism of action which supposes concomitant disruption of TSP-1:CD47 interaction and enhancement of CD36 activation by TSP-1, TAX2 may inhibit tumor progression while limiting many of the undesired side effects of broadly inhibiting important physiological functions of CD47."
"Inhibition of TSP-1 binding to either CD36 or CD47 using peptide mimics of the binding sites was investigated next."
"This might be of utmost importance for the contributions of endothelial cell-mediated angiogenesis following TSP-1 binding to CD36 and CD47."
"We studied two peptides interacting with CD36, CSVTCG and GDGV(dI)TRIR [11,16] and 4N1-1, one of the two CD47 binding sites of TSP-1 [15] ."
"These results indicate that that TSP-1 cell surface binding to CD36 and CD47 is essential for chemotaxis enhancement, and suggest that CD36 may be the more important of the TSP-1 receptors for enhancing chemotaxis to C5a."
"Binding of CD47 to other ligands such as integrins, TSP-1 and TSP-1-derived peptides, also involves the IgV domain of CD47 [ xref ]."
"In addition, TSP-1 can also bind to different integrins, CD47 and heparan sulfated proteoglycans [ xref ]."
"Because CD47 is known to associate laterally with other signaling receptors, including VEGFR2, and TSP1 binding to CD47 inhibits VEGFR2 signaling by dissociating CD47 xref , we hypothesized that interaction of CD47 with the CD14 complex might similarly modulate signal one."