Cancer Cell:内皮细胞Notch 1活性促进肿瘤转移

2017-06-14 海北 MedSci原创

肿瘤转移一直是癌症治疗中最令人头疼的事儿之一。对其机制的研究也是层出不穷。6月13日,德国科学家Andreas Fischer在肿瘤细胞(Caner Cell)上发文阐释内皮细胞和肿瘤转移之间的关系。

肿瘤转移一直是癌症治疗中最令人头疼的事儿之一。对其机制的研究也是层出不穷。613日,德国科学家Andreas Fischer在肿瘤细胞(Caner Cell)上发文阐释内皮细胞和肿瘤转移之间的关系。

内皮细胞能够产生血管分泌因子,协调肿瘤进展。Andreas Fischer课题组发现,在人类癌症和黑色素瘤的内皮细胞中,以及小鼠转移前肿瘤微环境中的内皮细胞上,经常能观察到活化的Notch 1受体。在黑色素瘤中,内皮细胞Notch 1受体的表达和较短的无进展生存期相关。此外,持续的Notch 1活化能够诱导内皮细胞的衰老,促使其表达趋化因子以及粘附因子VCAM 1。这会进一步促进嗜中性粒细胞的浸润,肿瘤细胞在内皮上的粘附、渗透、在肺部的聚集,以及术后转移。因此,种种迹象表明,持续的血管Notch信号激活通过产生一个衰老的促炎性内皮来促进肿瘤转移。

进而,利用Notch 1或是VCAM 1的阻断抗体治疗可以预防Notch诱导的肿瘤转移。在卵巢癌的小鼠模型中,利用基因手段破坏内皮细胞的Notch信号通路也可以抑制腹膜中性粒细胞的浸润。

原始出处:

Elfriede Wieland et al. Endothelial Notch1 Activity Facilitates Metastasis. 2017, Cancer Cell 31, 355–367. DOI: http://dx.doi.org/10.1016/j.ccell.2017.01.007

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    2017-10-16 维他命
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    2017-06-16 karmond
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    2017-06-16 ymljack

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