Selective upregulated expression of the α2-macroglobulin signaling receptor in highly metastatic 1-LN prostate carcinoma cells

Cellular binding of receptor-recognized forms of alpha (2)-macroglobulin (alpha M-2*) is mediated by the low-density lipoprotein receptor related protein (LRP) and the alpha M-2 signaling receptor (alpha 2MSR). In nonmalignant cells, ligation of alpha 2MSR promotes DNA synthesis and cellular proliferation. Here, we report that insulin treatment of highly metastatic I-LN human prostate carcinoma selectively increases alpha 2MSR expression and binding of alpha M-2* to 1-LN cells, alpha M-2* induces transient increases in intracellular calcium and inositol 1,4,5-trisphosphate in insulin-treated I-LN cells, consistent with activation of alpha 2MSR. Inhibition of signaling cascades activated by insulin blocks upregulation of alpha 2MSR. By contrast, alpha M-2* 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 alpha M-2* behaves like a growth factor in these highly malignant cells. The 1-LN metastatic phenotype may result, in part, from aberrant expression of alpha 2MSR, indicating the possible involvement of alpha M-2* in tumor progression. (C) 2000 Academic Press.