LRP-1 Matricellular Receptor Involvement in Triple Negative Breast Cancer Tumor Angiogenesis

• Published in: Biomedicines Vol. 9; no. 10; p. 1430
• Main Authors: Campion, Océane, Thevenard Devy, Jessica, Billottet, Clotilde, Schneider, Christophe, Etique, Nicolas, Dupuy, Jean-William, Raymond, Anne-Aurélie, Boulagnon Rombi, Camille, Meunier, Marie, Djermoune, El-Hadi, Lelièvre, Elodie, Wahart, Amandine, Bour, Camille, Hachet, Cathy, Cairo, Stefano, Bikfalvi, Andréas, Dedieu, Stéphane, Devy, Jérôme
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 01.10.2021; MDPI
• Subjects: Angiogenesis; Breast cancer; Computer Science; Gene expression; Growth factors; LRP-1; Magnetic resonance imaging; Medical research; Phenols; Plasmin; Proteomes; Proteomics; RNA-mediated interference; Scavenger receptors; Secretome; Signal and Image Processing; TNBC; Tumors; Xenografts; France; United States > US; Germany; breast cancer; LRP-1; TNBC; angiogenesis
• ISSN: 2227-9059; 2227-9059
• DOI: 10.3390/biomedicines9101430

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.