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- Title
LRP-1 Matricellular Receptor Involvement in Triple Negative Breast Cancer Tumor Angiogenesis.
- 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
- Abstract
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.
- Subjects
TRIPLE-negative breast cancer; BREAST tumors; CELLULAR signal transduction; NEOVASCULARIZATION; TUMOR growth
- Publication
Biomedicines, 2021, Vol 9, Issue 10, p1430
- ISSN
2227-9059
- Publication type
Article
- DOI
10.3390/biomedicines9101430