Alpha2-macroglobulin inhibits the malignant properties of astrocytoma cells by impeding beta-catenin signaling.
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.
Lindner
Inge
I
Institute of Biochemistry, Department of Ophthalmology, University of Leipzig, Leipzig, Germany.
Hemdan
Nasr Y A
NY
Buchold
Martin
M
Huse
Klaus
K
Bigl
Marina
M
Oerlecke
Ilka
I
Ricken
Albert
A
Gaunitz
Frank
F
Sack
Ulrich
U
Naumann
Andreas
A
Hollborn
Margrit
M
Thal
Dietmar
D
Gebhardt
Rolf
R
Birkenmeier
Gerd
G
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*
D026563:LDL-Receptor Related Protein-Associated Protein; D000511:alpha-Macroglobulins; D051176:beta Catenin