cell rep:伴随着衰老,乳腺癌风险增加?Cell子刊给出解释

2018-04-28 忐忑 生物探索

衰老与细胞成分的组织水平变化有关,这些变化会增加疾病的易感性。来自挪威、瑞士和美国的研究人员最新发现乳房组织中与年龄有关的差异,证实这些差异会增加年长女性患乳腺癌的风险。

衰老与细胞成分的组织水平变化有关,这些变化会增加疾病的易感性。来自挪威、瑞士和美国的研究人员最新发现乳房组织中与年龄有关的差异,证实这些差异会增加年长女性患乳腺癌的风险。

Breast sections of a 17 (left) and a 58 year old woman (right) stained for a luminal marker (green) and a myoepithelial/basal marker (red). The luminal cells lose fidelity with age which causes them to appear less luminal and more basal. High-dimensional analysis pinpointed this key age-related change in the luminal population, which may be associated with higher breast cancer risk. Credit: Jonathan K Lee in the lab of Dr. Mark LaBarge

这项研究结果以“High-Dimensional Phenotyping Identifies Age-Emergent Cells in Human Mammary Epithelia”为题发表在4月24日的《Cell Reports》杂志上,可能有助于科学家更好地理解在衰老过程中乳腺细胞的变化,从而使医生能够更早地发现癌症的征兆。DOI: https://doi.org/10.1016/j.celrep.2018.03.114

此前研究表明,随着女性年龄的增长,她们乳房组织的组成也发生了变化。考虑到多能祖细胞(Multipotent progenitors)能够发育成多种类型的细胞,并在体内积累。所以,科学家们怀疑,祖细胞的大量涌入会导致癌症。

“我们推测,这些祖细胞的积累是导致乳腺癌易感性增加的一种机制,” City of Hope的人口科学教授Mark LaBarge说。“我们在过去的数据中看到了这一点,并在最新的研究中第一次以如此高的分辨率识别到这些与年龄相关的差异。”

原始出处:
Pelissier Vatter FA, Schapiro D, Chang H, et al.High-Dimensional Phenotyping Identifies Age-Emergent Cells in Human Mammary Epithelia.Cell Rep. 2018 Apr 24;23(4):1205-1219. doi: 10.1016/j.celrep.2018.03.114.

由卑尔根大学生物医学教授James Lorens领导的国际小组研究了56名年龄在16-91岁之间女性的细胞。结果发现随着受试者年龄增加,多能祖细胞在乳腺组织上皮层积聚,并且会发展成有缺陷的腔细胞(luminal cells)。这些有缺陷的腔细胞看起来更像肌上皮(外)细胞,使整个管腔层的外观不太一致。与此同时,抑制肿瘤的肌上皮细胞比例减少。

“我们能够证明,与年龄有关的腔细胞是由有缺陷的管腔祖细胞(luminal progenitors)衍生而来的,而且它们会随着年龄的增长而积累。” Lorens说,“这项研究让我们更深入地了解随着年龄增长而发生的变化,并展示了乳腺上皮组细胞的异质性。”研究小组还识别出在衰老的乳腺细胞中出现的蛋白质特征,他们认为这一发现可能与老年女性对乳腺癌易感性的增加有直接关系。

值得注意的是,衰老细胞的外观变化以及这些变化所带来的健康威胁,并非乳腺组织所特有。研究人员发现,骨髓和大脑细胞也存在类似的年龄相关性差异。第一作者Fanny Pelissier Vatter说:“有倾斜分化和功能的干/祖细胞的积累可能是许多组织衰老的标志。”

研究人员使用算法创建上皮细胞表型的虚拟图,以此分析细胞样品的数据,并将更多相似外观的细胞组合在一起。这些视觉分组让研究团队能够识别不同年龄的乳房组织的微小变化,并指出不同的细胞是如何相关联的。反过来,他们可以根据组织中出现的上皮细胞类型,将女性分配到正确的年龄群中。这表明,这些细胞的差异与年龄有极强的相关性。唯一例外的是一组携带BRCA1基因的年轻女性的小细胞样本,她们的细胞更接近于老年女性的细胞。

研究人员认为,这些成果可以帮助医生们更好地了解乳腺组织及其周围的微环境是如何随着年龄的增长而发生改变的,进而可以预防癌症。“绘制衰老过程中不断变化的细胞表型,并将它们与早期癌症表型形成关联,可以发现潜在的干预点。”Lorens说道。

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    2018-04-29 维他命
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    2018-07-20 sjq027
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    2018-04-30 1209e435m98(暂无昵称)

    学习了.谢谢分享

    0

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    2018-04-29 kafei

    了解一下谢谢

    0

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    2018-04-28 1ddf0692m34(暂无匿称)

    学习了.长知识

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    2018-04-28 wzb521zf

    一起学习学习

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