title: The Matricellular Receptor LRP1 Forms an Interface for Signaling and Endocytosis in Modulation of the Extracellular Tumor Environment.
abstract: The membrane protein low-density lipoprotein receptor related-protein 1 (LRP1) has been attributed a role in cancer. However, its presumably often indirect involvement is far from understood. LRP1 has both endocytic and signaling activities. As a matricellular receptor it is involved in regulation, mostly by clearing, of various extracellular matrix degrading enzymes including matrix metalloproteinases, serine proteases, protease inhibitor complexes, and the endoglycosidase heparanase. Furthermore, by binding extracellular ligands including growth factors and subsequent intracellular interaction with scaffolding and adaptor proteins it is involved in regulation of various signaling cascades. LRP1 expression levels are often downregulated in cancer and some studies consider low LRP1 levels a poor prognostic factor. On the contrary, upregulation in brain cancers has been noted and clinical trials explore the use of LRP1 as cargo receptor to deliver cytotoxic agents. This mini-review focuses on LRP1's role in tumor growth and metastasis especially by modulation of the extracellular tumor environment. In relation to this role its diagnostic, prognostic and therapeutic potential will be discussed.
authors.affiliation: Laboratory for Experimental Mouse Genetics, Department of Human Genetics , KU Leuven, Leuven, Belgium.
authors.forename: Bart
authors.initials: B
authors.lastname: Van Gool
authors.affiliation: Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7369 Matrice Extracellulaire et Dynamique Cellulaire, Université de Reims Champagne-Ardenne, Unité de Formation et de Recherche Sciences Exactes et Naturelles , Reims, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Dedieu
authors.affiliation: Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7369 Matrice Extracellulaire et Dynamique Cellulaire, Université de Reims Champagne-Ardenne, Unité de Formation et de Recherche Sciences Exactes et Naturelles , Reims, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Emonard
authors.affiliation: Laboratory for Experimental Mouse Genetics, Department of Human Genetics , KU Leuven, Leuven, Belgium.
authors.forename: Anton J M
authors.initials: AJ
authors.lastname: Roebroek
keywords: LRP1; cancer; endocytosis; extracellular matrix; metastasis; signaling