LRP-1 matricellular receptor involvement in triple negative breast cancer tumor angiogenesis

Océane Campion (1) , Jessica Thevenard Devy (1) , Clotilde Billottet (2) , Christophe Schneider (1) , Nicolas Etique (1) , Jean-William Dupuy (3) , Anne-Aurélie Raymond (4) , Camille Boulagnon Rombi (1) , Marie Meunier (1) , El-Hadi Djermoune (5) , Elodie Lelièvre (1) , Amandine Wahart (1) , Camille Bour (1) , Cathy Hachet (1) , Stefano Cairo (6) , Andréas Bikfalvi (2) , Stéphane Dedieu (1) , Jérôme Devy (1)

1 MEDyC - Matrice Extracellulaire et Dynamique Cellulaire - UMR CNRS 7369
2 LAMC - Laboratoire Angiogenèse et Micro-environnement des Cancers
3 Plateforme Protéome [Bordeaux]
4 UMS3427 - INSERM US005 - TBM-Core [Bordeaux]
5 CRAN - Centre de Recherche en Automatique de Nancy
6 XenTech [Evry]

Background: LRP-1 is a multifunctional scavenger receptor belonging to the LDLR family. Due to its capacity to control pericellular levels of various growth factors and proteases, LRP-1 plays a crucial role in membrane proteome dynamics, which appears decisive for tumor progression. Methods: LRP-1 involvement in a TNBC model was assessed using an RNA interference strategy in MDA-MB-231 cells. In vivo, tumorigenic and angiogenic effects of LRP-1-repressed cells were evaluated using an orthotopic xenograft model and two angiogenic assays (Matrigel® plugs, CAM). DCE-MRI, FMT, and IHC were used to complete a tumor longitudinal follow-up and obtain morphological and functional vascular information. In vitro, HUVECs’ angiogenic potential was evaluated using a tumor secretome, subjected to a proteomic analysis to highlight LRP-1-dependant signaling pathways. Results: LRP-1 repression in MDA-MB-231 tumors led to a 60% growth delay because of, inter alia, morphological and functional vascular differences, confirmed by angiogenic models. In vitro, the LRP-1-repressed cells secretome restrained HUVECs’ angiogenic capabilities. A proteomics analysis revealed that LRP-1 supports tumor growth and angiogenesis by regulating TGF-β signaling and plasminogen/plasmin system. Conclusions: LRP-1, by its wide spectrum of interactions, emerges as an important matricellular player in the control of cancer-signaling events such as angiogenesis, by supporting tumor vascular morphology and functionality.

Mots clés: breast cancer; TNBC; LRP-1; angiogenesis

Domaines: Traitement du signal et de l'image [eess.SP]

Océane Campion, Jessica Thevenard Devy, Clotilde Billottet, Christophe Schneider, Nicolas Etique, et al.. LRP-1 matricellular receptor involvement in triple negative breast cancer tumor angiogenesis. Biomedicines, 2021, 9 (10), pp.1430. ⟨10.3390/biomedicines9101430⟩. ⟨hal-03373264v2⟩