Molecular Basis for the Regulation of Angiogenesis by Thrombospondin-1 and -2
Patrick R. Lawler,Jack Lawler +1 more
TLDR
Advances in understanding of the molecular regulation of angiogenesis by TSP have paved the way for innovations in experimental treatment of cancers and will likely continue to offer vast avenues for discovery in other disease processes as well.Abstract:
Thrombospondins TSP-1 and TSP-2 are potent endogenous inhibitors of angiogenesis. They inhibit angiogenesis through direct effects on endothelial cell migration, proliferation, survival, and apoptosis and by antagonizing the activity of VEGF. Several of the membrane receptor systems and signal transduction molecules that mediate the effects of TSP-1 and TSP-2 have been elucidated. TSP-1 and TSP-2 exert their direct effects through CD36, CD47, and integrins. Recent data indicate that CD36 and β1 integrins collaborate to transmit the signals that are initiated by TSP-1 and TSP-2. Furthermore, these receptors appear to associate with VEGFR2 to form a platform for the integration of positive and negative signals for angiogenesis. Cross talk between pro- and antiangiogenic signal transduction pathways may enable TSP-1 and TSP-2 to inhibit angiogenesis by antagonizing survival pathways while also activating apoptotic pathways. CD36 and CD47 are both involved in the suppression of nitric oxide (NO). Advances in understanding of the molecular regulation of angiogenesis by TSP have paved the way for innovations in experimental treatment of cancers and will likely continue to offer vast avenues for discovery in other disease processes as well.read more
Citations
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References
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TL;DR: This new capillary growth is even more vigorous and continuous than a similar outgrowth of capillary sprouts observed in 2016 and is likely to be accompanied by neovascularization.
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Patterns and Emerging Mechanisms of the Angiogenic Switch during Tumorigenesis
TL;DR: The work from the authors' laboratories reviewed herein was supported by grants from the National Cancer Institute.
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TL;DR: The extracellular matrix and ECM proteins are important in phenomena as diverse as developmental patterning, stem cell niches, cancer, and genetic diseases and these properties need to be incorporated into considerations of the functions of the ECM.
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TL;DR: Using a dosing schedule of cyclophosphamide that provided more sustained apoptosis of endothelial cells within the vascular bed of a tumor, it is shown that a chemotherapeutic agent can more effectively control tumor growth in mice, regardless of whether the tumor cells are drug resistant.
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Essential role of endothelial nitric oxide synthase for mobilization of stem and progenitor cells.
Alexandra Aicher,Christopher Heeschen,Christiane Mildner-Rihm,Carmen Urbich,Christian Ihling,Katja Technau-Ihling,Andreas M. Zeiher,S Dimmeler +7 more
TL;DR: It is indicated that eNOS expressed by bone marrow stromal cells influences recruitment of stem and progenitor cells, which may contribute to impaired regeneration processes in ischemic heart disease patients, who are characterized by a reduced systemic NO bioactivity.