Oncogene:卵巢癌是如何扩散的?

2017-06-28 枫丹白露 来宝网

每年有20,000次诊断,卵巢癌是美国妇女中第九大常见癌症和癌症死亡的第五大原因。这么多的女性因卵巢癌而死亡,因为它常常在骨盆和腹部扩散之前才被检出,至此难以治疗,通常是致命的。



研究阐明卵巢癌是如何扩散的】每年有20,000次诊断卵巢癌是美国妇女中第九大常见癌症和癌症死亡的第五大原因。这么多的女性因卵巢癌而死亡,因为它常常在骨盆和腹部扩散之前才被检出,至此难以治疗,通常是致命的。

加州大学河滨分校和圣母大学的一组研究人员正在研究卵巢癌扩散或转移的分子机制,以发现新的治疗机会。

在他们“癌基因”杂志上发表的最新文章中,他们使用活体成像和电子显微镜来研究与成功转移相关的细胞活性,包括一组称为钙粘蛋白的蛋白质的表达,这些蛋白质有助于细胞结合在一起。由于这些蛋白质能够使癌细胞锚定在体内的新位点,所以可能通过阻断钙粘蛋白介导的结合来破坏转移。研究由加州大学河滨分校应用数学杰出教授马克·阿尔伯德(Mark Alber)和生物化学学士Kleiderer-Pezold教授,巴黎圣母院哈珀癌症研究所所长M. Sharon Stack领导。

随着原发性卵巢肿瘤转移,它们将单个细胞和细胞簇(称为多细胞聚集体(MCAs))分解成骨盆和腹部。为了研究转移发生的准确性,研究人员量化了上皮性卵巢癌(EOC)细胞与腹壁三维模型的相互作用。他们表明,当EOC细胞获得N-cadherin(Ncad)时,它们可以穿透并附着在腹壁上。此外,MCA在入侵前分散为大量的细胞,显示成功转移需要细胞与细胞的连接完整性(即在单细胞水平附着)。

Alber说,与其他癌症观察到的结果不同,卵巢癌细胞似乎没有表现出“引导者跟踪”类型的集体细胞侵袭。

“有趣的是,Ncad表达细胞与表达E-钙粘蛋白(Ecad)的细胞的共培养不能促进表达Ecad的细胞的侵袭,”。

研究结果强调Ncad在卵巢癌转移中的重要性,并提供支持使用Ncad阻断分子作为抑制EOC转移锚定的治疗策略的临床前研究的理由。

该组正在使用这些结果开发癌细胞侵袭的计算模型。未来的研究还将使用患者样本,这将由加利福尼亚州杜阿尔市的合作者提供,用于组合建模和实验方法,以获得对卵巢癌转移的细胞机制的新见解。

原始出处:

Y Klymenko, O Kim, E Loughran,et al. Cadherin composition and multicellular aggregate invasion in organotypic models of epithelial ovarian cancer intraperitoneal metastasis. Oncogene , (19 June 2017) | doi:10.1038/onc.2017.171.

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    2017-08-10 cy0324
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    2017-07-03 日月生辉

    新的转移机制,必然带来新的治疗方式,学习了!

    0

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    2017-06-30 zsyan
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    2017-06-29 hfuym10906

    学习了。。。。

    0

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    2017-06-28 luominglian113

    学习了,谢谢分享

    0

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    2017-06-28 139****5926

    好文章学习了

    0

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    2017-06-28 1e145228m78(暂无匿称)

    学习了,谢谢作者分享!

    0

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