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α2-Macroglobulin Inhibits the Malignant Properties of Astrocytoma Cells by Impeding β-Catenin Signaling

Targets that could improve the treatment of brain tumors remain important to define. This study of a transformation-associated isoform of α2-macroglobulin (A2M*) and its interaction with the low-density lipoprotein receptor-related protein-1 (LRP1) suggests a new mechanism for abrogating the maligna...

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Published in:Cancer research (Chicago, Ill.) Ill.), 2010, Vol.70 (1), p.277-287
Main Authors: LINDNER, Inge, HEMDAN, Nasr Y. A, HOLLBORN, Margrit, THAL, Dietmar, GEBHARDT, Rolf, BIRKENMEIER, Gerd, BUCHOLD, Martin, HUSE, Klaus, BIGL, Marina, OERLECKE, Ilka, RICKEN, Albert, GAUNITZ, Frank, SACK, Ulrich, NAUMANN, Andreas
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Language:English
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Summary:Targets that could improve the treatment of brain tumors remain important to define. This study of a transformation-associated isoform of α2-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/β-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. Cancer Res; 70(1); 277–87
ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.CAN-09-1462