限制
癌变
表型
催乳素
内科学
肿瘤科
癌症研究
医学
生物
遗传学
癌症
基因
激素
工程类
机械工程
作者
Vanessa M. López‐Ozuna,Ibrahim Y. Hachim,Mahmood Y. Hachim,Jean Jacques Lebrun,Suhad Ali
出处
期刊:Endocrine-related Cancer
[Bioscientifica]
日期:2019-03-01
卷期号:26 (3): 321-337
被引量:13
摘要
Triple-negative breast cancer (TNBC) accounts for ~20% of all breast cancer cases. The management of TNBC represents a challenge due to its aggressive phenotype, heterogeneity and lack of targeted therapy. Loss of cell differentiation and enrichment with breast cancer stem-like cells (BCSC) are features of TNBC contributing to its aggressive nature. Here, we found that treatment of TNBC cells with PRL significantly depletes the highly tumorigenic BCSC subpopulations CD44+/CD24- and ALDH+ and differentiates them to the least tumorigenic CD44-/CD24- and ALDH- phenotype with limited tumorsphere formation and self-renewal capacities. Importantly, we found PRL to induce a heterochromatin phenotype marked by histone H3 lysine 9 trimethylation (H3K9me3) and accompanied by ultra-structural cellular architecture associated with differentiation and senescence rendering the cells refractory to growth signals. Crucially, we found PRL to mediate these effects in vivo in a pre-clinical animal xenograft of TNBC controlling tumor growth. These results reveal that the lactogenic hormone PRL may exert its anti-tumorigenic effects on TNBC through cellular reprogramming indicative of differentiation resulting in the depletion of BCSCs and restricting tumorigenesis.
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