Archiv - Januar 2010

Alpha2-macroglobulin inhibits the malignant properties of astrocytoma cells by impeding beta-catenin signaling.

Lindner I, Hemdan NY, Buchold M, Huse K, Bigl M, Oerlecke I, Ricken A, Gaunitz F, Sack U, Naumann A, Hollborn M, Thal D, Gebhardt R, Birkenmeier G.

Institute of Biochemistry, Department of Ophthalmology, University of Leipzig, Leipzig, Germany.

Cancer Res. 2010 Jan 1;70(1):277-87

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.

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