Wong Grace L, Abu Jalboush Sara, Lo Hui-Wen
Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, NC 27101, USA.
Wake Forest Comprehensive Cancer Center, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Cancers (Basel). 2020 Jul 7;12(7):1827. doi: 10.3390/cancers12071827.
Breast cancer is the most frequent malignancy for women in which one in eight women will be diagnosed with the disease in their lifetime. Despite advances made in treating primary breast cancer, there is still no effective treatment for metastatic breast cancer. Consequently, metastatic breast cancer is responsible for 90% of breast cancer-related deaths while only accounting for approximately one third of all breast cancer cases. To help develop effective treatments for metastatic breast cancer, it is important to gain a deeper understanding of the mechanisms by which breast cancer metastasizes, particularly, those underlying organotropism towards brain, bone, and lungs. In this review, we will primarily focus on the roles that circulating exosomal microRNAs (miRNAs) play in organotropism of breast cancer metastasis. Exosomes are extracellular vesicles that play critical roles in intercellular communication. MicroRNAs can be encapsulated in exosomes; cargo-loaded exosomes can be secreted by tumor cells into the tumor microenvironment to facilitate tumor-stroma interactions or released to circulation to prime distant organs for subsequent metastasis. Here, we will summarize our current knowledge on the biogenesis of exosomes and miRNAs, mechanisms of cargo sorting into exosomes, the exosomal miRNAs implicated in breast cancer metastasis, and therapeutic exosomal miRNAs.
乳腺癌是女性中最常见的恶性肿瘤,八分之一的女性在其一生中会被诊断出患有这种疾病。尽管在原发性乳腺癌的治疗方面取得了进展,但转移性乳腺癌仍然没有有效的治疗方法。因此,转移性乳腺癌导致了90%的乳腺癌相关死亡,而其病例数仅占所有乳腺癌病例的约三分之一。为了帮助开发针对转移性乳腺癌的有效治疗方法,深入了解乳腺癌转移的机制,特别是那些导致乳腺癌向脑、骨和肺发生器官趋向性转移的机制非常重要。在这篇综述中,我们将主要关注循环外泌体微小RNA(miRNA)在乳腺癌转移器官趋向性中所起的作用。外泌体是细胞外囊泡,在细胞间通讯中发挥关键作用。微小RNA可以被包裹在外泌体中;携带货物的外泌体可以由肿瘤细胞分泌到肿瘤微环境中,以促进肿瘤-基质相互作用,或者释放到循环系统中,为远处器官的后续转移做好准备。在这里,我们将总结我们目前对外泌体和微小RNA的生物发生、外泌体货物分选机制、与乳腺癌转移相关的外泌体微小RNA以及治疗性外泌体微小RNA的认识。