Ir. Asplin et al., Selective upregulated expression of the alpha(2)-macroglobulin signaling receptor in highly metastatic 1-LN prostate carcinoma cells, ARCH BIOCH, 383(1), 2000, pp. 135-141
Cellular binding of receptor-recognized forms of alpha (2)-macroglobulin (a
lpha M-2*) is mediated by the low-density lipoprotein receptor related prot
ein (LRP) and the alpha M-2 signaling receptor (alpha 2MSR). In nonmalignan
t cells, ligation of alpha 2MSR promotes DNA synthesis and cellular prolife
ration. Here, we report that insulin treatment of highly metastatic I-LN hu
man prostate carcinoma selectively increases alpha 2MSR expression and bind
ing 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 signalin
g cascades activated by insulin blocks upregulation of alpha 2MSR. By contr
ast, 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 t
hat alpha M-2* behaves like a growth factor in these highly malignant cells
. The 1-LN metastatic phenotype may result, in part, from aberrant expressi
on of alpha 2MSR, indicating the possible involvement of alpha M-2* in tumo
r progression. (C) 2000 Academic Press.