乳腺癌脑转移过程中乳腺癌衍生微RNA与脑微环境细胞之间的相互影响

Munazza Khan, Grace L Wong, Chuling Zhuang, Mariana K. Najjar, Hui-Wen Lo
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摘要

乳腺癌是女性最常见的恶性肿瘤,占美国新诊断癌症总数的 15.2%。远处乳腺癌转移是乳腺癌相关死亡的主要原因;脑转移是乳腺癌转移的第三大常见部位,但预后最差,仅能存活约 8 个月。目前针对乳腺癌脑转移(BCBM)的治疗方案有限且效果不佳。为了帮助确定治疗乳腺癌脑转移的有效新疗法,研究乳腺癌细胞转移到大脑并在大脑微环境中茁壮成长的机制非常重要。为此,有研究报告称,原发性乳腺肿瘤细胞可通过释放细胞外囊泡-微RNA(miRNA),为包括星形胶质细胞和小胶质细胞在内的脑部微环境细胞提供能量,促进BCBM的形成。乳腺肿瘤衍生的 miRNA 还能通过破坏脑微血管内皮细胞的完整性,促进乳腺癌细胞通过血脑屏障入侵。在这篇综述中,我们总结了目前有关乳腺癌衍生的促进血脑屏障的 miRNA 的文献,介绍了它们在血脑屏障的复杂步骤中的作用,特别是它们与脑转移龛内微环境细胞的相互作用,最后讨论了它们在治疗血脑屏障中的应用。
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Crosstalk between breast cancer-derived microRNAs and brain microenvironmental cells in breast cancer brain metastasis
Breast cancer is the most frequent malignancy in women, constituting 15.2% of all new cancers diagnosed in the United States. Distant breast cancer metastasis accounts for the majority of breast cancer-related deaths; brain metastasis is the third most common site for metastatic breast cancer but is associated with worst prognosis of approximately eight months of survival. Current treatment options for breast cancer brain metastasis (BCBM) are limited and ineffective. To help identify new and effective therapies for BCBM, it is important to investigate the mechanisms by which breast cancer cells metastasize to the brain and thrive in the brain microenvironment. To this end, studies have reported that primary breast tumor cells can prime brain microenvironmental cells, including, astrocytes and microglia, to promote the formation of BCBM through the release of extracellular vesicle-microRNAs (miRNAs). Breast tumor-derived miRNAs can also promote breast cancer cell invasion through the blood-brain barrier by disrupting the integrity of the brain microvascular endothelial cells. In this review, we summarize current literature on breast cancer-derived BCBM-promoting miRNAs, cover their roles in the complex steps of BCBM particularly their interactions with microenvironmental cells within the brain metastatic niche, and finally discuss their therapeutic applications in the management of BCBM.
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