CD36 A critical anti angiogenic receptor

Simantov, Ronit; Silverstein, Roy L.

doi:10.2741/1168

Cited by 74 publications

(59 citation statements)

References 67 publications

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“…In this assay, plates are coated with the recombinant TSR + RFK proteins and varying amounts of a recombinant version of the CLESH (CD36, LIMPII, Emp sequence homology; amino acids 95−143 of human CD36) domain of CD36, which is fluorescently labeled, are incubated in the plates. The CLESH domain has been shown by others to mediate the binding of TSP-1 to CD36 [55]. As shown in Fig.…”

Section: Tsr2 ± Rfk Inhibits Tumor Growth and Metastasismentioning

confidence: 87%

The effect of thrombospondin-1 on breast cancer metastasis

Yee

Connolly

Duquette

et al. 2008

Breast Cancer Res Treat

112

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Thrombospondin-1 (TSP-1) has been proposed to have both pro-metastatic and anti-metastatic properties. To elucidate its role in breast cancer metastasis, we compared tumor progression in the polyomavirus middle T antigen (Pyt) transgenic mouse and the TSP-1-null Pyt transgenic mouse. We characterized the tumors in these mice at 45, 60 and 90 days of age. Tumor size, areas of necrosis, macrophage infiltration, levels of active and total TGF-β, vessel morphology, and lung and blood metastasis were measured in these mice. Mammary tumors were larger in the TSP-1-null mouse, and vessels were larger, but fewer in number in these tumors. The level of total TGF-β was significantly higher in the Pyt tumors at 90 days of age. Importantly, significantly fewer metastases were observed in the lungs of the TSP-1-null/Pyt mouse. Primary Pyt tumor cells were more migratory than TSP-1-null Pyt tumor cells on collagen. Treatment of Pyt mice with recombinant proteins that contain the type-1 repeats of TSP-1 resulted in decreased primary tumor growth and metastasis. Sequences that are involved in CD36 binding and those required for TGF-β activation mediated the inhibition of primary tumor growth. Thus, TSP-1 in the mammary tumor microenvironment inhibits angiogenesis and tumor growth, but promotes metastasis to the lung in the Pyt transgenic mouse. The ability of TSP-1 to support metastasis correlates with its ability to promote tumor cell migration.

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Section: Tsr2 ± Rfk Inhibits Tumor Growth and Metastasismentioning

confidence: 87%

The effect of thrombospondin-1 on breast cancer metastasis

Yee

Connolly

Duquette

et al. 2008

Breast Cancer Res Treat

112

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“…57 The angiopoietin receptor TEK/Tie2 exerts tight control on angiogenesis (maintaining them quiescent on angiopoetin-1 binding, but promoting endothelial cell activation on angiopoietin-2 binding) and has also been suggested to localize in endothelial cell caveolae. 58 CD36 is a critical anti-angiogenic receptor of endothelial cells 59 which co-fractionates with caveolae and co-immunoprecipitates with caveolin-1. 60 This suggests that caveolin-1, and caveolae, may regulate angiogenesis by multiple pathways, including NO-mediated and NO-independent mechanisms (Figure 7).…”

Section: Discussionmentioning

confidence: 99%

Altered Angiogenesis in Caveolin-1 Gene–Deficient Mice Is Restored by Ablation of Endothelial Nitric Oxide Synthase

Morais

Ebrahem

Anand‐Apte

et al. 2012

The American Journal of Pathology

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Caveolin-1 is an essential structural protein of caveolae, specialized plasma membrane organelles highly abundant in endothelial cells, where they regulate multiple functions including angiogenesis. Caveolin-1 exerts a tonic inhibition of endothelial nitric oxide synthase (eNOS) activity. Accordingly, caveolin-1 gene-disrupted mice have enhanced eNOS activity as well as increased systemic nitric oxide (NO) levels. We hypothesized that excess eNOS activity, secondary to caveolin deficiency, would mediate the decreased angiogenesis observed in caveolin-1 gene-disrupted mice. We tested tumor angiogenesis in mice lacking either one or both proteins, using in vitro, ex vivo, and in vivo assays. We show that endothelial cell migration, tube formation, cell sprouting from aortic rings, tumor growth, and angiogenesis are all significantly impaired in both caveolin-1-null and eNOSnull mice. We further show that these parameters were either partially or fully restored in double knockout mice that lack both caveolin-1 and eNOS. Furthermore, the effects of genetic ablation of eNOS are mimicked by the administration of the NOS inhibitor N-nitro-L-arginine methyl ester hydrochloride (L-NAME), including the reversal of the caveolin-1-null mouse angiogenic phenotype. This study is the first to demonstrate the detrimental effects of unregulated eNOS activity on angiogenesis, and shows that impaired tumor angiogenesis in caveolin-1-null mice is, at least in part, the result of enhanced eNOS activity.

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“…Recent studies in tumor biology indicate that TSP-1 and one of its receptors (CD36) possess antiangiogenic capacities (Armstrong & Bornstein 2003, Simantov & Silverstein 2003. However, the role of TSP-1 is controversial and estrogens seem to induce this factor in breast cancer cells, indicating that it may have additional functions in the breast (S M Hyder, unpublished observation).…”

Section: Potential Sex-steroid Targets For Anti-angiogenic Therapy Ofmentioning

confidence: 99%

Sex-steroid regulation of vascular endothelial growth factor in breast cancer

Hyder¹

2006

Endocr Relat Cancer

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Angiogenesis is a key event, which occurs in both normal and pathological expansion of tissues and provides the nourishment necessary for growth. The role of angiogenic growth factors in breast pathology is rapidly gaining recognition since scientists and clinicians realized that these factors could function as molecular targets event 550 209822 for controlling tumor expansion. Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis. Although significant advances have been made in understanding the sex-steroid-dependent regulation of this key factor, the role of VEGF in controlling breast tumors is not well understood. In this review, I discuss recent studies describing the role of the female sex steroids estrogens and progestins in the regulation of VEGF in breast cancer cells. Furthermore, I present a summary of recent studies from other biological systems (mainly focused on tumor biology) directed towards providing us with a better understanding of the regulation of classical VEGF and VEGF receptors. I propose that by extending such studies we will gain deeper insights into how we might combat the progression of breast cancer by controlling hormonedependent angiogenesis within tumor tissue. I believe that information gained from such studies will permit us to target angiogenic growth factors and their initiated signal transduction pathways in a more precise and selective manner, and thereby to control the formation of new blood vessels that fuel the rapid growth of breast tumors. Finally, it is my hope that the concepts discussed here will help elucidate molecular targets in the hormone-dependent angiogenesis pathway that will ultimately allow us to overcome anti-hormone resistance and to provide insights into how we might pursue the concept of chemoprevention by considering 'angioprevention' as the end point.

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CD36 A critical anti angiogenic receptor

Cited by 74 publications

References 67 publications

The effect of thrombospondin-1 on breast cancer metastasis

The effect of thrombospondin-1 on breast cancer metastasis

Altered Angiogenesis in Caveolin-1 Gene–Deficient Mice Is Restored by Ablation of Endothelial Nitric Oxide Synthase

Sex-steroid regulation of vascular endothelial growth factor in breast cancer

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