Academic Journal
Targeting the Urotensin II/UT G Protein-Coupled Receptor to Counteract Angiogenesis and Mesenchymal Hypoxia/Necrosis in Glioblastoma
| Title: | Targeting the Urotensin II/UT G Protein-Coupled Receptor to Counteract Angiogenesis and Mesenchymal Hypoxia/Necrosis in Glioblastoma |
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| Authors: | Le Joncour, Vadim, Guichet, Pierre-Olivier, Dembélé, Kleouforo-Paul, Mutel, Alexandre, Campisi, Daniele, Perzo, Nicolas, Desrues, Laurence, Modzelewski, Romain, Couraud, Pierre-Olivier, Honnorat, Jérôme, Ferracci, François-Xavier, Marguet, Florent, Laquerrière, Annie, Vera, Pierre, Bohn, Pierre, Langlois, Olivier, Morin, Fabrice, Gandolfo, Pierrick, Castel, Hélène |
| Contributors: | Equipe Quantification en Imagerie Fonctionnelle (LITIS - QuantIF), Laboratoire d'Informatique, de Traitement de l'Information et des Systèmes (LITIS), Université Le Havre Normandie (ULH), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Université Le Havre Normandie (ULH), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA) |
| Source: | ISSN: 2296-634X ; Frontiers in Cell and Developmental Biology ; https://hal.science/hal-03222754 ; Frontiers in Cell and Developmental Biology, 2021, 9, pp.652544. ⟨10.3389/fcell.2021.652544⟩. |
| Publisher Information: | CCSD Frontiers media |
| Publication Year: | 2021 |
| Collection: | Normandie Université: HAL |
| Subject Terms: | urotensin II, necrosis, glioblastoma, biased ligand, angiogenesis, UT receptor, [SDV]Life Sciences [q-bio] |
| Description: | International audience ; Glioblastomas (GBMs) are the most common primary brain tumors characterized by strong invasiveness and angiogenesis. GBM cells and microenvironment secrete angiogenic factors and also express chemoattractant G protein-coupled receptors (GPCRs) to their advantage. We investigated the role of the vasoactive peptide urotensin II (UII) and its receptor UT on GBM angiogenesis and tested potential ligand/therapeutic options based on this system. On glioma patient samples, the expression of UII and UT increased with the grade with marked expression in the vascular and peri-necrotic mesenchymal hypoxic areas being correlated with vascular density. In vitro human UII stimulated human endothelial HUV-EC-C and hCMEC/D3 cell motility and tubulogenesis. In mouse-transplanted Matrigel sponges, mouse (mUII) and human UII markedly stimulated invasion by macrophages, endothelial, and smooth muscle cells. In U87 GBM xenografts expressing UII and UT in the glial and vascular compartments, UII accelerated tumor development, favored hypoxia and necrosis associated with increased proliferation (Ki67), and induced metalloproteinase (MMP)-2 and -9 expression in Nude mice. UII also promoted a “tortuous” vascular collagen-IV expressing network and integrin expression mainly in the vascular compartment. GBM angiogenesis and integrin αvβ3 were confirmed by in vivo 99m Tc-RGD tracer imaging and tumoral capture in the non-necrotic area of U87 xenografts in Nude mice. Peptide analogs of UII and UT antagonist were also tested as potential tumor repressor. Urotensin II-related peptide URP inhibited angiogenesis in vitro and failed to attract vascular and inflammatory components in Matrigel in vivo . Interestingly, the UT antagonist/biased ligand urantide and the non-peptide UT antagonist palosuran prevented UII-induced tubulogenesis in vitro and significantly delayed tumor growth in vivo. Urantide drastically prevented endogenous and UII-induced GBM angiogenesis, MMP, and integrin activations, associated with GBM ... |
| Document Type: | article in journal/newspaper |
| Language: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/33937253; PUBMED: 33937253; PUBMEDCENTRAL: PMC8079989 |
| DOI: | 10.3389/fcell.2021.652544 |
| Availability: | https://hal.science/hal-03222754 https://hal.science/hal-03222754v1/document https://hal.science/hal-03222754v1/file/fcell-09-652544.pdf https://doi.org/10.3389/fcell.2021.652544 |
| Rights: | https://creativecommons.org/licenses/by/4.0/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: | edsbas.4552E6C5 |
| Database: | BASE |
| DOI: | 10.3389/fcell.2021.652544 |
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