Growth-suppressing function of glypican-3 (GPC3) via insulin like growth factor II (IGF-II) signaling pathway in ovarian clear cell carcinoma cells
Growth-suppressing function of glypican-3 (GPC3) via insulin like growth factor II (IGF-II) signaling pathway in ovarian clear cell carcinoma cells
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DOI：
10.1016/j.ygyno.2010.07.013
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发表时间：
2010-11-01
影响因子：
4.7
通讯作者：
Kikkawa, Fumitaka
中科院分区：
文献类型：
--
作者：
Sakurai, Maiko;Shibata, Kiyosumi;Kikkawa, Fumitaka
Objective.众所周知，卵巢透明细胞癌（CCC）对铂类化疗具有高度耐药性。磷脂酰肌醇蛋白聚糖-3（GPC 3），一种膜结合硫酸乙酰肝素蛋白聚糖，仅在上皮性卵巢癌亚型的CCC中过表达。本研究的目的是确定在卵巢CC的作用。为了评估GPC 3在卵巢癌CCC细胞中的功能，我们建立了一种稳定转染包含靶向GPC 3的shRNA质粒的卵巢癌细胞系KOC 7 C细胞（shGPC细胞），并比较了细胞生长和克隆形成能力与对照shRNA转染细胞（shCon细胞）。我们发现，shGPC 3细胞显着增加细胞生长和集落形成的潜力相比，shCon细胞在1%血清含100 ng/ml IGF-II的培养基。此外，这些影响显着减弱预处理与1 μ M渥曼青霉素（抑制剂PI 3 K/Akt）。我们首次证明了CCC细胞中存在与细胞生长抑制相关的升高水平的GPC 3蛋白。我们的数据表明，GPC 3有可能成为卵巢CCC患者的新的治疗靶点。(C)2010年爱思唯尔公司All rights reserved.
Objective. Ovarian clear cell carcinoma (CCC) is well known to be highly resistant to platinum-based chemotherapy. Glypican-3 (GPC3), a membrane-bound heparan sulfate proteoglycan, is overexpressed in only CCC of epithelial ovarian carcinoma subtypes. The purpose of this study was to identify the role of GPO in ovarian CCC.Methods. To evaluate the function of GPC3 in ovarian CCC cells, we generated an ovarian cancer cell line, KOC7C cells stably transfected with plasmids encompassing shRNA targeting GPC3 (shGPC cells), and compared cell growth and the colony-forming ability to control shRNA-transfected cells (shCon cells).Results. We showed that shGPC3 cells significantly increased cell growth and the colony-forming potential compared with shCon cells in 1% serum containing medium with 100 ng/ml IGF-II. Furthermore, these effects were significantly attenuated by pretreatment with 1 mu M wortmannin (an inhibitor of PI3K/Akt).Conclusions. We have demonstrated for the first time the presence of elevated levels of GPC3 protein associated with cell growth inhibition in CCC cells. Our data suggest that GPC3 has the potential to become a novel therapeutic target for ovarian CCC patients. (C) 2010 Elsevier Inc. All rights reserved.