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Proteoglycans of basement membranes: Crucial controllers of angiogenesis, neurogenesis, and autophagy.
Mongiat, Maurizio; Pascal, Gabriel; Poletto, Evelina; Williams, Davion M; Iozzo, Renato V.
Afiliación
  • Mongiat M; Department of Research and Diagnosis, Division of Molecular Oncology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, 33081 Aviano, Italy.
  • Pascal G; Department of Pathology and Genomic Medicine, and the Translational Cellular Oncology Program, Sidney Kimmel Cancer Center, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA 19107, USA.
  • Poletto E; Department of Research and Diagnosis, Division of Molecular Oncology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, 33081 Aviano, Italy.
  • Williams DM; Department of Pathology and Genomic Medicine, and the Translational Cellular Oncology Program, Sidney Kimmel Cancer Center, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA 19107, USA.
  • Iozzo RV; Department of Pathology and Genomic Medicine, and the Translational Cellular Oncology Program, Sidney Kimmel Cancer Center, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA 19107, USA.
Proteoglycan Res ; 2(3)2024.
Article en En | MEDLINE | ID: mdl-39184370
ABSTRACT
Anti-angiogenic therapy is an established method for the treatment of several cancers and vascular-related diseases. Most of the agents employed target the vascular endothelial growth factor A, the major cytokine stimulating angiogenesis. However, the efficacy of these treatments is limited by the onset of drug resistance. Therefore, it is of fundamental importance to better understand the mechanisms that regulate angiogenesis and the microenvironmental cues that play significant role and influence patient treatment and outcome. In this context, here we review the importance of the three basement membrane heparan sulfate proteoglycans (HSPGs), namely perlecan, agrin and collagen XVIII. These HSPGs are abundantly expressed in the vasculature and, due to their complex molecular architecture, they interact with multiple endothelial cell receptors, deeply affecting their function. Under normal conditions, these proteoglycans exert pro-angiogenic functions. However, in pathological conditions such as cancer and inflammation, extracellular matrix remodeling leads to the degradation of these large precursor molecules and the liberation of bioactive processed fragments displaying potent angiostatic activity. These unexpected functions have been demonstrated for the C-terminal fragments of perlecan and collagen XVIII, endorepellin and endostatin. These bioactive fragments can also induce autophagy in vascular endothelial cells which contributes to angiostasis. Overall, basement membrane proteoglycans deeply affect angiogenesis counterbalancing pro-angiogenic signals during tumor progression, and represent possible means to develop new prognostic biomarkers and novel therapeutic approaches for the treatment of solid tumors.
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Texto completo: 1 Base de datos: MEDLINE Idioma: En Revista: Proteoglycan Res Año: 2024 Tipo del documento: Article País de afiliación: Italia

Texto completo: 1 Base de datos: MEDLINE Idioma: En Revista: Proteoglycan Res Año: 2024 Tipo del documento: Article País de afiliación: Italia