Endostatin and endorepellin: A common route of action for similar angiostatic cancer avengers

Poluzzi, Chiara; Iozzo, Renato V.; Schaefer, Liliana

doi:10.1016/j.addr.2015.10.012

Cited by 109 publications

(90 citation statements)

References 277 publications

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“…Given its widespread distribution [124,125] and its ability to interact with various molecules perlecan regulates various biological processes. Either via the protein core or the heparan sulfate chains, perlecan binds other ECM components as laminin, fibronectin and ECM1 and several growth factors including Fibroblast Growth Factor 1 (FGF-1), FGF-2, FGF-7, FGF-9 and FGF-18, FGF-binding protein, Platelet-Derived Growth Factor (PDGF), Hepatocyte Growth Factor (HGF), activin A, VEGF and progranulin [126,127,128,129,130,131,132]. The central role of perlecan in angiogenesis has been demonstrated by several independent studies and in various in vitro and in vivo models [133,134,135].…”

Section: Proteoglycans: Complex Functions From the Protein Core Anmentioning

confidence: 99%

Extracellular Matrix, a Hard Player in Angiogenesis

Mongiat

Andreuzzi

Tarticchio

et al. 2016

IJMS

164

133

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The extracellular matrix (ECM) is a complex network of proteins, glycoproteins, proteoglycans, and polysaccharides. Through multiple interactions with each other and the cell surface receptors, not only the ECM determines the physical and mechanical properties of the tissues, but also profoundly influences cell behavior and many physiological and pathological processes. One of the functions that have been extensively explored is its impingement on angiogenesis. The strong impact of the ECM in this context is both direct and indirect by virtue of its ability to interact and/or store several growth factors and cytokines. The aim of this review is to provide some examples of the complex molecular mechanisms that are elicited by these molecules in promoting or weakening the angiogenic processes. The scenario is intricate, since matrix remodeling often generates fragments displaying opposite effects compared to those exerted by the whole molecules. Thus, the balance will tilt towards angiogenesis or angiostasis depending on the relative expression of pro- or anti-angiogenetic molecules/fragments composing the matrix of a given tissue. One of the vital aspects of this field of research is that, for its endogenous nature, the ECM can be viewed as a reservoir to draw from for the development of new more efficacious therapies to treat angiogenesis-dependent pathologies.

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Section: Proteoglycans: Complex Functions From the Protein Core Anmentioning

confidence: 99%

Extracellular Matrix, a Hard Player in Angiogenesis

Mongiat

Andreuzzi

Tarticchio

et al. 2016

IJMS

164

133

View full text Add to dashboard Cite

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“…That is to say, it is possible that vessel formation might be controlled in different ways when angiogenesis is acting as the “enemy” such as in cancer or in pathologies such as diabetic retinopathy (28), compared with situations like fracture healing where angiogenesis is the “friend” (29). Considering the large body of evidence now linking Dcn inhibition of angiogenesis to autophagy (30,31), we can not ignore the fact that Bgn could regulate autophagy during fracture healing. Indeed in this regard it is interesting to note that endostatin induces autophagy in endothelial cells by modulating Beclin 1 and beta-catenin (32).…”

Section: Discussionmentioning

confidence: 99%

Biglycan potentially regulates angiogenesis during fracture repair by altering expression and function of endostatin

et al. 2016

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The small proteoglycan biglycan (Bgn) is highly expressed in the organic matrix of bone and plays a role in bone formation. Previous work implicated Bgn in vessel growth during bone healing (1). By infusing barium sulfate (BaSO4) into WT and Bgn-deficient mice we discovered the positive effect of Bgn in modulating angiogenesis during fracture healing. Using micro-computed tomography angiography we found significant differences in the vessel size and volume among other parameters. To further understand the mechanistic basis for this, we explored the relationship between Bgn and the anti-angiogenic protein endostatin. Immunohistochemistry (IHC) showed co-localization of Bgn and endostatin in regions of bone formation, with increased endostatin staining in Bgn-KO compared to WT at 14 days post-fracture. To further elucidate the relationship between Bgn and endostatin, an endothelial cell tube formation assay was used. This study showed that endothelial cells treated with endostatin had significantly decreased vessel length and vessel branches compared to untreated cells, while cells treated with endostatin and Bgn at a 1:1 molar ratio had vessel length and vessel branches comparable to untreated cells. This indicated that Bgn was able to mitigate the inhibitory effect of endostatin on endothelial cell growth. In summary, these results suggest that Bgn is needed for proper blood vessel formation during fracture healing, and one mechanism by which Bgn impacts angiogenesis is through inhibition of endostatin.

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“…For instance, hydrolysis of types XV and XVIII collagens results in the generation of endostatin, an inhibitor of angiogenesis [110,111,112], and the cleavage of the α3 chain of type IV collagen by MMPs releases the fragment tumstatin, which is a potent anti-angiogenic molecule [113,114]. Another BM-derived fragment is endorepelin, the C-terminal fragment of perlecan, which also exerts anti-angiogenic activity [115]. Since SVMPs release fragments of all of these proteins in the exudates [15,24,40,41,48], it is suggested that some of them exert anti-angiogenic activity and influence the tissue repair process.…”

Section: Hydrolysis Of Ecm Proteins Alters Cell-matrix Interactionmentioning

confidence: 99%

A Comprehensive View of the Structural and Functional Alterations of Extracellular Matrix by Snake Venom Metalloproteinases (SVMPs): Novel Perspectives on the Pathophysiology of Envenoming

Gutiérrez

Escalante

Rucavado

et al. 2016

Toxins

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Snake venom metalloproteinases (SVMPs) affect the extracellular matrix (ECM) in multiple and complex ways. Previously, the combination of various methodological platforms, including electron microscopy, histochemistry, immunohistochemistry, and Western blot, has allowed a partial understanding of such complex pathology. In recent years, the proteomics analysis of exudates collected in the vicinity of tissues affected by SVMPs has provided novel and exciting information on SVMP-induced ECM alterations. The presence of fragments of an array of ECM proteins, including those of the basement membrane, has revealed a complex pathological scenario caused by the direct action of SVMPs. In addition, the time-course analysis of these changes has underscored that degradation of some fibrillar collagens is likely to depend on the action of endogenous proteinases, such as matrix metalloproteinases (MMPs), synthesized as a consequence of the inflammatory process. The action of SVMPs on the ECM also results in the release of ECM-derived biologically-active peptides that exert diverse actions in the tissue, some of which might be associated with reparative events or with further tissue damage. The study of the effects of SVMP on the ECM is an open field of research which may bring a renewed understanding of snake venom-induced pathology.

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Endostatin and endorepellin: A common route of action for similar angiostatic cancer avengers

Cited by 109 publications

References 277 publications

Extracellular Matrix, a Hard Player in Angiogenesis

Extracellular Matrix, a Hard Player in Angiogenesis

Biglycan potentially regulates angiogenesis during fracture repair by altering expression and function of endostatin

A Comprehensive View of the Structural and Functional Alterations of Extracellular Matrix by Snake Venom Metalloproteinases (SVMPs): Novel Perspectives on the Pathophysiology of Envenoming

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