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Cancer Cell:利用癌细胞善变,转化为脂肪细胞,一切都和谐了

2019-01-17 皮皮象 医世象

把癌细胞变成脂肪细胞?听上去非常的不可思议,但是瑞士巴塞尔大学Gerhard Christofori教授所率领的研究团队做到了!他们利用一种抗癌药和一种糖尿病药,竟真的把乳腺癌细胞变成了脂肪细胞,并且有效的抑制了癌症的转移。   这项研究于2019年1月14日,发表在癌症研究领域顶级学术期刊《Cancer Cell》上。研究团队证明,利用癌细胞善于“变化”的特性,可以将其诱导转化为脂

把癌细胞变成脂肪细胞?听上去非常的不可思议,但是瑞士巴塞尔大学Gerhard Christofori教授所率领的研究团队做到了!他们利用一种抗癌药和一种糖尿病药,竟真的把乳腺癌细胞变成了脂肪细胞,并且有效的抑制了癌症的转移。

这项研究于2019年1月14日,发表在癌症研究领域顶级学术期刊《Cancer Cell》上。研究团队证明,利用癌细胞善于“变化”的特性,可以将其诱导转化为脂肪细胞。在多种乳腺癌小鼠模型中,研究人员利用MEK抑制剂Trametinib和抗糖尿病药物罗格列酮进行联合治疗,癌细胞不仅真的转化成了脂肪细胞,而且原发性病灶的侵袭、传播以及转移都得到了有效抑制。

把癌细胞变成脂肪细胞,不得不说,这群科学家的脑洞真大啊!这项概念验证性研究有望为癌症患者的治疗提供一个全新的选择!

我们知道,癌细胞狡猾如狐,对自身所处的微环境十分敏感,稍有风吹草动,就立马进入一种“随时变身”的状态,转分化成为不同类型的细胞。而实现这一过程,是因为癌细胞具有高超的上皮-间质转化(EMT)本领。

EMT/MET过程,帮助癌细胞转移

EMT主要表现为上皮细胞通过特定程序转化为具有间质表型的细胞。EMT对于胚胎的发育十分重要,在胚胎形成过程中,干细胞通过EMT分化成为人体各类细胞。此外,EMT在组织再生中也发挥着重要作用,如帮助伤口愈合等。

但是,癌细胞同样也掌握了这一技能,来帮助自身实现侵袭和转移。由于EMT的发生,癌细胞具有了类似干细胞的能力,能够转化成多种类型的癌细胞,表现出极性丧失、黏附性降低、迁移能力增强,并发生远端转移。不仅如此,出EMT外,癌细胞还能逆向进行间质-上皮转化(MET),更加如虎添翼。

既然癌细胞如此善变,那为何不干脆把它们全部诱骗成安全、无害的脂肪细胞呢?基于以往经验以及不断的优化药物配方,瑞士巴塞尔大学的研究人员终于实现了这一目标,将癌细胞转化成为了“货真价实”的脂肪细胞!

与癌细胞相比,人畜无害的脂肪细胞

在尝试了多种药物方案后,研究人员发现,糖尿病药物罗格列酮和骨形态发生蛋白-2(BMP2)共同作用下,癌细胞能高效的转化生成脂肪细胞!

罗格列酮与BMP2作用,癌细胞生成脂肪细胞过程

进一步的分析表明,TGF-β信号通路在EMT/MET过程中,会抑制脂肪细胞的转化,而BMP2在此过程中,通过细胞周期调控主要影响了脂肪细胞的生成。

这些都帮助研究人员指向了另一个叫做MEK的关键蛋白,他们发现,如果能够抑制MEK的功能,就可以促进脂肪细胞的形成。幸运的是,早在2013年,美国FDA就已经批准了一款叫做Trametinib的MEK抑制剂上市!

体内实验表明,接受糖尿病药物罗格列酮和Trametinib联合治疗的小鼠,肿瘤的侵袭性显著降低,癌细胞不仅分化成为脂肪细胞,而且原发病灶几乎完全停止了全身转移!

 罗格列酮+Trametinib治疗,有效抑制了肿瘤侵袭

人源肿瘤小鼠移植模型的试验长期观察结果依旧令人满意,变成脂肪细胞的癌细胞一直“老老实实”的保持在脂肪细胞的状态,并没有重新转变为癌细胞。

癌细胞再也无法入侵周围组织啦!

染色结果表明,癌细胞被成功转化成了脂肪细胞

研究人员强调,这种治疗方法有望破坏肿瘤细胞对常规化疗的耐药性。接下来的,他们将开展进一步的试验,检测这种疗法与化疗,或其他癌症治疗方法联合的治疗效果。

原始出处:

Ishay-Ronen D, Diepenbruck M, Kalathur RKR, Sugiyama N, Tiede S, Ivanek R, Bantug G, Morini MF, Wang J, Hess C, Christofori G. Gain Fat-Lose Metastasis: Converting Invasive Breast Cancer Cells into Adipocytes Inhibits Cancer Metastasis. Cancer Cell. 2019 Jan 14;35(1):17-32.e6.

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    2019-09-29 维他命
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    2019-01-19 yxch36
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    2019-01-17 明月清辉

    谢谢分享,学习了

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