Asplin I R, Misra U K, Gawdi G, Gonzalez-Gronow M, Pizzo S V
Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Arch Biochem Biophys. 2000 Nov 1;383(1):135-41. doi: 10.1006/abbi.2000.2052.
Cellular binding of receptor-recognized forms of alpha2-macroglobulin (alpha2M*) is mediated by the low-density lipoprotein receptor related protein (LRP) and the alpha2M signaling receptor (alpha2MSR). In nonmalignant cells, ligation of alpha2MSR promotes DNA synthesis and cellular proliferation. Here, we report that insulin treatment of highly metastatic 1-LN human prostate carcinoma selectively increases alpha2MSR expression and binding of alpha2M* to 1-LN cells. alpha2M* induces transient increases in intracellular calcium and inositol 1,4,5-trisphosphate in insulin-treated 1-LN cells, consistent with activation of alpha2MSR. Inhibition of signaling cascades activated by insulin blocks upregulation of alpha2MSR. By contrast, alpha2M* 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 alpha2M* behaves like a growth factor in these highly malignant cells. The 1-LN metastatic phenotype may result, in part, from aberrant expression of alpha2MSR, indicating the possible involvement of alpha2M* in tumor progression.
受体识别形式的α2-巨球蛋白（α2M*）的细胞结合由低密度脂蛋白受体相关蛋白（LRP）和α2M信号受体（α2MSR）介导。在非恶性细胞中，α2MSR的连接促进DNA合成和细胞增殖。在此，我们报告胰岛素处理高转移性1-LN人前列腺癌可选择性增加α2MSR表达以及α2M与1-LN细胞的结合。α2M可诱导胰岛素处理的1-LN细胞内钙和肌醇1,4,5-三磷酸短暂增加，这与α2MSR的激活一致。抑制胰岛素激活的信号级联反应可阻断α2MSR的上调。相比之下，α2M不与PC-3细胞结合，也不诱导其细胞内信号传导，尽管1-LN细胞是从PC-3细胞亚克隆而来。我们认为α2M在这些高恶性细胞中表现得像一种生长因子。1-LN转移表型可能部分源于α2MSR的异常表达，这表明α2M*可能参与肿瘤进展。
