School of Pharmacy and Pharmaceutical Sciences & Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland;
School of Biomolecular and Biomedical Science, University College Dublin Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland.
Clin Chem. 2015 Dec;61(12):1457-65. doi: 10.1373/clinchem.2015.240028. Epub 2015 Oct 14.
Although it has been long realized that eukaryotic cells release complex vesicular structures into their environment, only in recent years has it been established that these entities are not merely junk or debris, but that they are tailor-made specialized minimaps of their cell of origin and of both physiological and pathological relevance. These exosomes and microvesicles (ectosomes), collectively termed extracellular vesicles (EVs), are often defined and subgrouped first and foremost according to size and proposed origin (exosomes approximately 30-120 nm, endosomal origin; microvesicles 120-1000 nm, from the cell membrane). There is growing interest in elucidating the relevance and roles of EVs in cancer.
Much of the pioneering work on EVs in cancer has focused on breast cancer, possibly because breast cancer is a leading cause of cancer-related deaths worldwide. This review provides an in-depth summary of such studies, supporting key roles for exosomes and other EVs in breast cancer cell invasion and metastasis, stem cell stimulation, apoptosis, immune system modulation, and anti-cancer drug resistance. Exosomes as diagnostic, prognostic, and/or predictive biomarkers and their potential use in the development of therapeutics are discussed.
Although not fully elucidated, the involvement of exosomes in breast cancer development, progression, and resistance is becoming increasingly apparent from preclinical and clinical studies, with mounting interest in the potential exploitation of these vesicles for breast cancer biomarkers, as drug delivery systems, and in the development of future novel breast cancer therapies.
尽管人们早就意识到真核细胞会向其环境中释放复杂的囊泡结构，但直到最近几年，人们才确定这些囊泡并非仅仅是垃圾或碎片，而是其起源细胞及其生理和病理相关性的特制微型地图。这些外泌体和微泡（ectosomes），统称为细胞外囊泡（EVs），通常首先根据大小和推测的起源进行定义和分组（外泌体约 30-120nm，起源于内体；微泡 120-1000nm，起源于细胞膜）。人们越来越关注 EVs 在癌症中的相关性和作用。
在癌症的 EVs 研究中，大部分开创性工作都集中在乳腺癌上，这可能是因为乳腺癌是全球癌症相关死亡的主要原因。本综述深入总结了此类研究，支持外泌体和其他 EVs 在乳腺癌细胞侵袭和转移、干细胞刺激、细胞凋亡、免疫系统调节和抗癌药物耐药性中的关键作用。还讨论了外泌体作为诊断、预后和/或预测生物标志物及其在治疗药物开发中的潜在用途。
尽管尚未完全阐明，但越来越多的临床前和临床研究表明，外泌体参与了乳腺癌的发生、发展和耐药性，人们对这些囊泡作为乳腺癌生物标志物、药物传递系统以及开发未来新型乳腺癌治疗方法的潜在应用产生了浓厚的兴趣。
