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

Cancer Res. 2010 Jan 1;70(1):277-87. doi: 10.1158/0008-5472.CAN-09-1462.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Astrocytoma / metabolism*
  • Blotting, Western
  • Cell Adhesion / physiology
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Cell Proliferation
  • Gene Expression
  • Humans
  • Immunohistochemistry
  • LDL-Receptor Related Protein-Associated Protein / metabolism*
  • Signal Transduction / physiology*
  • alpha-Macroglobulins / metabolism*
  • beta Catenin / metabolism*


  • LDL-Receptor Related Protein-Associated Protein
  • alpha-Macroglobulins
  • beta Catenin