title: Alpha2-macroglobulin inhibits the malignant properties of astrocytoma cells by impeding beta-catenin signaling.
abstract: Targets that could improve the treatment of brain tumors remain important to define. This study of a transformation-associated isoform of alpha2-macroglobulin (A2M*) and its interaction with the low-density lipoprotein receptor-related protein-1 (LRP1) suggests a new mechanism for abrogating the malignant potential of astrocytoma cells. LRP1 bound A2M* found to be associated with an inhibition of tumor cell proliferation, migration, invasion, spheroid formation, and anchorage-independent growth. Transcriptional studies implicated effects on the Wnt/beta-catenin signaling pathway. Notably, LRP1 antibodies could phenocopy the effects of A2M*. Our findings suggest a pathway of tumor suppression in astrocytoma that might be tractable to therapeutic exploitation.
authors.affiliation: Institute of Biochemistry, Department of Ophthalmology, University of Leipzig, Leipzig, Germany.
authors.forename: Inge
authors.initials: I
authors.lastname: Lindner
authors.forename: Nasr Y A
authors.initials: NY
authors.lastname: Hemdan
authors.forename: Martin
authors.initials: M
authors.lastname: Buchold
authors.forename: Klaus
authors.initials: K
authors.lastname: Huse
authors.forename: Marina
authors.initials: M
authors.lastname: Bigl
authors.forename: Ilka
authors.initials: I
authors.lastname: Oerlecke
authors.forename: Albert
authors.initials: A
authors.lastname: Ricken
authors.forename: Frank
authors.initials: F
authors.lastname: Gaunitz
authors.forename: Ulrich
authors.initials: U
authors.lastname: Sack
authors.forename: Andreas
authors.initials: A
authors.lastname: Naumann
authors.forename: Margrit
authors.initials: M
authors.lastname: Hollborn
authors.forename: Dietmar
authors.initials: D
authors.lastname: Thal
authors.forename: Rolf
authors.initials: R
authors.lastname: Gebhardt
authors.forename: Gerd
authors.initials: G
authors.lastname: Birkenmeier
mesh_terms: D001254:Astrocytoma / Q000378:metabolism*; D015153:Blotting, Western; D002448:Cell Adhesion / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D026563:LDL-Receptor Related Protein-Associated Protein / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D000511:alpha-Macroglobulins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D026563:LDL-Receptor Related Protein-Associated Protein; D000511:alpha-Macroglobulins; D051176:beta Catenin