Construction and characteristics of an E-cadherin-related three-dimensional suspension growth model of ovarian cancer.
Construction and characteristics of an E-cadherin-related three-dimensional suspension growth model of ovarian cancer.
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E-cadherin相关卵巢癌三维悬浮生长模型的构建及特点
DOI：
10.1038/srep05646
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发表时间：
2014-07-10
影响因子：
4.6
通讯作者：
Liu L
中科院分区：
文献类型：
--
作者：
Xu S;Yang Y;Dong L;Qiu W;Yang L;Wang X;Liu L
卵巢癌是所有妇科恶性肿瘤中最致命的。转移性卵巢癌细胞主要以多细胞球体（MCS）的形式存在于晚期卵巢癌患者的腹水中。我们假设E-钙粘蛋白作为一种重要的细胞粘附分子，可能在MCS的形成和存活中发挥重要作用。因此，我们建立了表达高水平E-cadherin的卵巢癌细胞的三维悬浮培养模型，通过CCK-8检测研究其生长、增殖和对化疗药物的耐药性。与E-cadherin表达低或缺失的细胞形成的细胞悬液团相比，E-cadherin表达高的SKOV-3细胞的MCS体积更大、细胞连接更紧密、存活时间更长。尽管所有三种细胞系的悬浮细胞团均增殖停滞，可能是由于细胞周期停滞在G1/S，但与没有E-钙粘蛋白表达的SKOV-3细胞和具有低E-钙粘蛋白表达的OVCAR-3细胞相比，高E-钙粘蛋白SKOV-3细胞在顺铂处理后72 小时的细胞死亡率显着降低。因此，我们得出结论，E-钙粘蛋白在卵巢癌 MCS 形成、维持和耐药性中发挥着至关重要的作用，并且可能成为晚期卵巢癌治疗的潜在靶点。
Ovarian cancer is the deadliest of all gynecologic malignancies. Metastatic ovarian cancer cells exist mainly in the form of multi-cellular spheroids (MCSs) in the ascites of patients with advanced ovarian cancer. We hypothesized that E-cadherin, as an important cell-adhesion molecule, might play an important role in the formation and survival of MCSs. Therefore, we established a three-dimensional suspension culture model of ovarian cancer cells that express high levels of E-cadherin to investigate their growth, proliferation and resistance to chemotherapeutic drugs by CCK-8 assays. Compared to the cell suspension masses formed by cells with low or absent E-cadherin expression, the MCSs of high E-cadherin SKOV-3 cells had larger volumes, tighter cellular connections and longer survival times. Although the suspension cell masses of all three cell lines were proliferatively stagnant, possibly due to cell cycle arrest at G1/S, cell mortality at 72 h after cisplatin treatment was significantly decreased in the high E-cadherin SKOV-3 cells compared to SKOV-3 cells without E-cadherin expression and to OVCAR-3 cells with low E-cadherin expression. We conclude, therefore, E-cadherin plays a vital role in MCS formation, maintenance and drug resistance in ovarian cancer and could be a potential target for late-stage ovarian cancer treatment.