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通过抑制胰岛素样生长因子II/甘露糖-6-磷酸受体降低前列腺癌细胞迁移

Decreased prostate cancer cell migration by inhibition of the insulin-like growth factor II/Mannose-6-Phosphate receptor.

作者信息

Evans C P, Elfman F, Cunha G, Shuman M A

机构信息

Department of Urology, University of California, Davis School of Medicine, Sacramento, CA USA.

出版信息

Urol Oncol. 1997 Sep-Dec;3(5-6):166-70. doi: 10.1016/s1078-1439(98)00020-9.

DOI:10.1016/s1078-1439(98)00020-9
PMID:21227140
Abstract

The 270-kDa insulin-like growth factor II (IGF-II)/cation-independent mannose-6-phosphate receptor (MPR) is a multifunctional receptor protein. Endocytoses and intracellular transport of soluble enzymes bearing mannose6-phosphate (M-6-P) residues to lysosomes is mediated by the IGF-II/MPR. We examined human prostate cancer cells for IGF-II/MPR expression to determine whether this receptor mediates cell migration. PC3 human prostate cancer cells were studied for intracellular IGF-II/MPR by immunoblotting. PC3 cell surface IGF-II/MPR expression was assessed by flow cytometric analysis. Cell motility was quantitated by a scratch migration assay, and IGF-II/MPR blockade was achieved using M-6-P or affinity-purified rabbit anti-bovine cation-independent IGF-II/MPR immunoglobulin. IGF-II/MPR is expressed in the cytoplasm and on the surface of PC3 prostate cancer cells. The mean number of PC3 cells migrating per high powered field in medium containing polyclonal anti-IGF-II/MPR immunoglobulin or M-6-P decreased significantly (5 ± 4 cells and 34 ± 5 cells, respectively) compared with control medium containing mouse immunoglobulin G (70 ± 12 cells) or mannose-1-phosphate (67 ± 7 cells). This decreased PC3 cell migration following cell surface IGF-II/MPR blockade suggests that the IGF-II/MPR may play an important role in prostate cancer cell motility.

摘要

270 kDa的胰岛素样生长因子II(IGF-II)/不依赖阳离子的甘露糖-6-磷酸受体(MPR)是一种多功能受体蛋白。带有甘露糖6-磷酸(M-6-P)残基的可溶性酶向溶酶体的内吞作用和细胞内运输由IGF-II/MPR介导。我们检测了人前列腺癌细胞中IGF-II/MPR的表达,以确定该受体是否介导细胞迁移。通过免疫印迹法研究了PC3人前列腺癌细胞中的细胞内IGF-II/MPR。通过流式细胞术分析评估PC3细胞表面IGF-II/MPR的表达。通过划痕迁移试验对细胞运动性进行定量,使用M-6-P或亲和纯化的兔抗牛不依赖阳离子的IGF-II/MPR免疫球蛋白实现IGF-II/MPR阻断。IGF-II/MPR在PC3前列腺癌细胞的细胞质和表面均有表达。与含有小鼠免疫球蛋白G(70±12个细胞)或甘露糖-1-磷酸(67±7个细胞)的对照培养基相比,在含有多克隆抗IGF-II/MPR免疫球蛋白或M-6-P的培养基中,每个高倍视野迁移的PC3细胞平均数显著减少(分别为5±4个细胞和34±5个细胞)。细胞表面IGF-II/MPR阻断后PC3细胞迁移减少,这表明IGF-II/MPR可能在前列腺癌细胞运动中起重要作用。

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