Signals leading to apoptosis-dependent inhibition of neovascularization by thrombospondin-1

Jiménez, Benilde; Volpert, Olga V.; Crawford, Susan E.; Febbraio, Maria; Silverstein, Roy L.; Bouck, Noël

doi:10.1038/71517

Cited by 945 publications

(876 citation statements)

References 45 publications

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“…High endothelial cell proliferation in slow growing tumours may be balanced by apoptosis and vascular regression. 26 Studies have confirmed that endothelial cells in human cancers also have a higher proliferative index compared with other organs despite the much slower growth rate of human tumours compared with experimental ones. [27][28][29][30] These observations and our findings support the notion that anti-vascular therapy targeted at proliferating endothelium is likely to prove efficacious in human tumours.…”

Section: Discussionmentioning

confidence: 96%

Reduced growth in response to ganciclovir treatment of subcutaneous xenografts expressing HSV-tk in the vascular compartment

Mavria

2001

Gene Ther

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Using a recombinant retrovirus with ecotropic envelope we have achieved high efficiency of transduction of endothelial cells in the vasculature of subcutaneous xenografts arising from the co-injection of tumour cells and irradiated virus producers. We have used this experimental system to assess the efficacy of the herpes simplex virus-thymidine kinase (HSV-tk)/ganciclovir (GCV) prodrug activation system in anti-vascular therapy. Treatment of KSY-1 xenografts with HSV-tk transduction in the vascular compartment with the Sphase-dependent drug GCV resulted in extensive haemorrhagic necrosis, indicative of vascular damage. Therapeutic potential in tumours with transduced endothelial cells comprising 5% or less of the total tumour mass was similar to that of tumours with HSV-tk expression in over 46% of

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Section: Discussionmentioning

confidence: 96%

Reduced growth in response to ganciclovir treatment of subcutaneous xenografts expressing HSV-tk in the vascular compartment

Mavria

2001

Gene Ther

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“…In addition to facilitating fatty acid transport into adipocytes and cardiac and skeletal muscle (and perhaps other cells), CD36 was recently shown to be a sensor for fatty acids in taste buds, eliciting a secretory response in the gut (Laugerette, et al, 2005). CD36 interacts with ligands which contain a thrombospondin 1 (TSP-1) type 1 repeat element (TSR) to inhibit a pro-angiogenic signal, resulting in endothelial cell apoptosis (Dawson, Pearce, Zhong, Silverstein, Frazier, & Bouck, 1997,Dawson, et al, 1999,Jimenez, Volpert, Crawford, Febbraio, Silverstein, & Bouck, 2000,Miao, Seng, Duquette, Lawler, Laus, & Lawler, 2001,Simantov, Febbraio & Silverstein, 2005.…”

Section: Cd36 Structure and Expressionmentioning

confidence: 99%

“…On CD36, the TSP-interacting domain has been mapped to the CLESH-1 domain (CD36, LIMPII, emp, SR-BI homology) which is also present in other proteins (Crombie, & Silverstein, 1998). Work from our lab in collaboration with Noel Bouck demonstrated that in endothelial cells, when CD36 binds to TSP-1 there is association with and phosphorylation of the src kinase fyn, and this leads to downstream phosphorylation of caspases and the mitogen activated protein (MAP) kinase p38, and ultimately cellular apoptosis which prevents angiogenesis (Figure 1a) (Jimenez, Volpert, Crawford, Febbraio, Silverstein, & Bouck, 2000). Primo et al, (2005) using site directed mutagenesis to create C-terminal tail mutants of CD36 expressed in human umbilical vein endothelial cells by a retroviral vector, showed that specific amino acids, cysteine 464, arginine 467 and lysine 469, were essential to the TSP-1 inhibitory activity.…”

Section: Cd36 Signalingmentioning

confidence: 99%

CD36: Implications in cardiovascular disease

Febbraio

Silverstein

2007

The International Journal of Biochemistry & Cell Biology

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215

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CD36 is a broadly expressed membrane glycoprotein that acts as a facilitator of fatty acid uptake, a signaling molecule, and a receptor for a wide range of ligands, including apoptotic cells, modified forms of low density lipoprotein, thrombospondins, fibrillar beta-amyloid, components of gram positive bacterial walls and malaria infected erythrocytes. CD36 expression on macrophages, dendritic and endothelial cells, and in tissues including muscle, heart, and fat, suggest diverse roles, and indeed, this is truly a multifunctional receptor involved in both homeostatic and pathologic conditions. Despite an impressive increase in our knowledge of CD36 functions, in depth understanding of the mechanistic aspects of this protein remains elusive. This review focuses on CD36 in cardiovascular disease-what we know, and what we have yet to learn.

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“…It was initially isolated from platelets and megakaryocytes [28], but was later detected in several cell types such as macrophages and adipocytes [21,22,30,32]. Nowadays, it is known that TSP-1 is a multifunctional protein composed by multiple structural domains [5,10], and it has been especially related with several anti-angiogenic pathways [20,23,24].…”

Section: Introductionmentioning

confidence: 99%

Glucose and insulin modify thrombospondin 1 expression and secretion in primary adipocytes from diet-induced obese rats

et al. 2011

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Thrombospondin 1 (TSP-1), an anti-angiogenic factor and TGF-β activity regulator, has been recently recognized as an adipokine that correlates with obesity, inflammation and insulin-resistance processes. In the present study, epididymal adipocytes of rats that were fed a chow (C) or a high fat diet (HFD) for 50 days, were isolated and incubated (24-72 h) in low (LG; 5.6 mM) or high (HG; 25 mM) glucose, in presence or absence of 1.6 nM insulin. Rats fed the HF diet showed an established obesity state. Serum TSP-1 levels and TSP-1 mRNA basal expression of adipocytes from HFD rats were higher than those from controls. Adipocytes from HFD animals presented an insulin-resistance state, as suggested by the lower insulin-stimulated glucose uptake as compared to controls. TSP-1 expression in culture was higher in adipocytes from obese animals at 24 h, but when the adipocytes were treated with HG, these expression levels dropped dramatically. Later at 72 h, TSP-1 expression was lower in adipocytes from HFD rats, and no effects of the other treatments were observed. Surprisingly, the secretion levels of this protein at 72 h were increased significantly by the HG treatment in both types of adipocytes, although they were even higher in adipocytes from obese animals. Finally, cell viability was significantly reduced by HG treatment in both types of adipocytes. In summary, TSP-1 expression/secretion was modulated in an in vitro model of insulinresistant adipocytes. The difference between expression and secretion patterns suggests a post-transcriptional regulation. The present study confirms that TPS-1 is closely associated with obesity-related mechanisms.

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Signals leading to apoptosis-dependent inhibition of neovascularization by thrombospondin-1

Cited by 945 publications

References 45 publications

Reduced growth in response to ganciclovir treatment of subcutaneous xenografts expressing HSV-tk in the vascular compartment

Reduced growth in response to ganciclovir treatment of subcutaneous xenografts expressing HSV-tk in the vascular compartment

CD36: Implications in cardiovascular disease

Glucose and insulin modify thrombospondin 1 expression and secretion in primary adipocytes from diet-induced obese rats

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