title: Cellular Cholesterol Distribution Influences Proteolytic Release of the LRP-1 Ectodomain.
abstract: Low-density lipoprotein receptor-related protein-1 (LRP-1) is a multifunctional matricellular receptor composed of a large ligand-binding subunit (515-kDa α-chain) associated with a short trans-membrane subunit (85-kDa β-chain). LRP-1, which exhibits both endocytosis and cell signaling properties, plays a key role in tumor invasion by regulating the activity of proteinases such as matrix metalloproteinases (MMPs). LRP-1 is shed at the cell surface by proteinases such as membrane-type 1 MMP (MT1-MMP) and a disintegrin and metalloproteinase-12 (ADAM-12). Here, we show by using biophysical, biochemical, and cellular imaging approaches that efficient extraction of cell cholesterol and increased LRP-1 shedding occur in MDA-MB-231 breast cancer cells but not in MDA-MB-435 cells. Our data show that cholesterol is differently distributed in both cell lines; predominantly intracellularly for MDA-MB-231 cells and at the plasma membrane for MDA-MB-435 cells. This study highlights the relationship between the rate and cellular distribution of cholesterol and its impact on LRP-1 shedding modulation. Altogether, our data strongly suggest that the increase of LRP-1 shedding upon cholesterol depletion induces a higher accessibility of the sheddase substrate, i.e., LRP-1, at the cell surface rather than an increase of expression of the enzyme.
authors.affiliation: Laboratoire de Signalisation et Récepteurs Matriciels, UFR de Sciences Exactes et Naturelles, Université de Reims Champagne-ArdenneReims, France; CNRS, Matrice Extracellulaire et Dynamique Cellulaire, UMR 7369Reims, France.
authors.forename: Bassil
authors.initials: B
authors.lastname: Dekky
authors.affiliation: Laboratoire de Signalisation et Récepteurs Matriciels, UFR de Sciences Exactes et Naturelles, Université de Reims Champagne-ArdenneReims, France; CNRS, Matrice Extracellulaire et Dynamique Cellulaire, UMR 7369Reims, France.
authors.forename: Amandine
authors.initials: A
authors.lastname: Wahart
authors.affiliation: Laboratoire de Signalisation et Récepteurs Matriciels, UFR de Sciences Exactes et Naturelles, Université de Reims Champagne-ArdenneReims, France; CNRS, Matrice Extracellulaire et Dynamique Cellulaire, UMR 7369Reims, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Sartelet
authors.affiliation: CNRS, Matrice Extracellulaire et Dynamique Cellulaire, UMR 7369Reims, France; MéDIAN-Biophotonique et Technologies pour la Santé, UFR de Pharmacie, Université de Reims Champagne-ArdenneReims, France; Plateforme d'Imagerie Cellulaire et Tissulaire, Université de Reims Champagne-ArdenneReims, France.
authors.forename: Michaël
authors.initials: M
authors.lastname: Féré
authors.affiliation: CNRS, Matrice Extracellulaire et Dynamique Cellulaire, UMR 7369Reims, France; MéDIAN-Biophotonique et Technologies pour la Santé, UFR de Pharmacie, Université de Reims Champagne-ArdenneReims, France; Plateforme d'Imagerie Cellulaire et Tissulaire, Université de Reims Champagne-ArdenneReims, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Angiboust
authors.affiliation: Laboratoire de Signalisation et Récepteurs Matriciels, UFR de Sciences Exactes et Naturelles, Université de Reims Champagne-ArdenneReims, France; CNRS, Matrice Extracellulaire et Dynamique Cellulaire, UMR 7369Reims, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Dedieu
authors.affiliation: CNRS, Matrice Extracellulaire et Dynamique Cellulaire, UMR 7369Reims, France; MéDIAN-Biophotonique et Technologies pour la Santé, UFR de Pharmacie, Université de Reims Champagne-ArdenneReims, France; Plateforme d'Imagerie Cellulaire et Tissulaire, Université de Reims Champagne-ArdenneReims, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Piot
authors.affiliation: Laboratoire de Signalisation et Récepteurs Matriciels, UFR de Sciences Exactes et Naturelles, Université de Reims Champagne-ArdenneReims, France; CNRS, Matrice Extracellulaire et Dynamique Cellulaire, UMR 7369Reims, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Devy
authors.affiliation: Laboratoire de Signalisation et Récepteurs Matriciels, UFR de Sciences Exactes et Naturelles, Université de Reims Champagne-ArdenneReims, France; CNRS, Matrice Extracellulaire et Dynamique Cellulaire, UMR 7369Reims, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Emonard
keywords: LRP-1; Raman microspectroscopy; cholesterol; ectodomain; low-density lipoprotein receptor-related protein-1; shedding