Neuropilin-1 promotes unlimited growth of ovarian cancer by evading contact inhibition
Neuropilin-1 promotes unlimited growth of ovarian cancer by evading contact inhibition
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DOI：
10.1016/j.ygyno.2007.02.005
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发表时间：
2007-06-01
影响因子：
4.7
通讯作者：
Fujii, Shingo
中科院分区：
文献类型：
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作者：
Baba, Tsukasa;Kariya, Masatoshi;Fujii, Shingo
Objective.神经纤毛蛋白-1（NRP-1）是脑信号蛋白和血管内皮生长因子的受体，在多种人类癌症中上调。虽然有一些报道NRP-1在卵巢肿瘤中的表达，但这些结果在其表达模式上有所不同，其在卵巢癌中的作用仍不清楚。我们试图研究NRP-1在卵巢癌中的表达模式和作用。采用免疫组织化学方法检测87例卵巢组织标本中NRP-1的表达，采用定量RT-PCR和Western blotting方法检测4种卵巢细胞系中NRP-1的表达。为探讨其在卵巢癌中的分子作用，采用WST-1实验、侵袭实验和软琼脂实验检测了NRP-1的表达。与卵巢表面上皮（OSE）、良性腺瘤和低度恶性肿瘤相比，NRP-1在卵巢癌中的表达增强。在体外，NRP-1的表达增加了三倍，在OSE细胞与癌基因ras的恶性转化，表明NRP-1和肿瘤发生之间的关联。NRP-1的抑制降低了致密状态下的细胞增殖，表明卵巢癌中NRP-1的持续高表达通过逃避接触抑制来增强增殖。NRP-1的抑制也降低了细胞在软琼脂中的生长和体外对细胞外基质的侵袭。这些结果表明，NRP-1不仅与肿瘤发生有关，而且与卵巢癌恶性程度有关，并且该分子是治疗卵巢恶性肿瘤的靶向候选物。(c)2007年爱思唯尔公司All rights reserved.
Objective. Neuropilin-1 (NRP-1) is a receptor for both semaphorin and vascular endothelial growth factor and is up-regulated in a variety of human cancers. While there are some reports of NRP-1 expression in ovarian neoplasm, those results differ in pattern of its expression and its role in ovarian cancer is still unclear. We sought to investigate the expression pattern and role of NRP-1 in ovarian cancer.Methods. NRP-1 expression was analyzed with eighty-seven ovarian tissue samples by immunohistochemistry and four ovarian cell lines by quantitative RT-PCR and Western blotting. To detect its molecular role in ovarian cancer, WST-1 assay, invasion assay and soft agar assay were performed with or without NRP-1 suppression by the introduction of short hairpin RNAs.Results. NRP-1 expression was found to be enhanced in ovarian cancer compared with ovarian surface epithelium (OSE), benign adenoma and tumors of low malignant potential. In vitro, NRP-1 expression was augmented threefold during malignant transformation of OSE cells with oncogene ras, suggesting an association between NRP-1 and oncogenesis. Suppression of NRP-1 reduced cell proliferation in a dense state, indicating that persistently high expression of NRP-1 in ovarian cancer enhances proliferation through evasion of contact inhibition. Suppression of NRP-1 also decreased cell growth in soft agar and invasion to the extracellular matrix in vitro.Conclusions. These results suggest that NRP-1 is not only associated with oncogenesis, but also with ovarian cancer malignancy, and this molecule is a targeting candidate for the treatment of ovarian malignancies. (c) 2007 Elsevier Inc. All rights reserved.