Selective Upregulated Expression of the α2-Macroglobulin Signaling Receptor in Highly Metastatic 1-LN Prostate Carcinoma Cells

Abstract

Cellular binding of receptor-recognized forms of α2-macroglobulin (α2M*) is mediated by the low-density lipoprotein receptor related protein (LRP) and the α2M signaling receptor (α2MSR). In nonmalignant cells, ligation of α2MSR promotes DNA synthesis and cellular proliferation. Here, we report that insulin treatment of highly metastatic 1-LN human prostate carcinoma selectively increases α2MSR expression and binding of α2M* to 1-LN cells. α2M* induces transient increases in intracellular calcium and inositol 1,4,5-trisphosphate in insulin-treated 1-LN cells, consistent with activation of α2MSR. Inhibition of signaling cascades activated by insulin blocks upregulation of α2MSR. By contrast, α2M* does not bind to nor induce intracellular signaling in PC-3 cells, even though 1-LN cells were subcloned from PC-3 cells. We suggest that α2M* behaves like a growth factor in these highly malignant cells. The 1-LN metastatic phenotype may result, in part, from aberrant expression of α2MSR, indicating the possible involvement of α2M* in tumor progression.