School of Pharmacy, Graduate School of Health Level 13, Building 1, University of Technology, Sydney, 123 Broadway, NSW, 2007, Australia.
Mol Cancer. 2012 Jun 8;11:37. doi: 10.1186/1476-4598-11-37.
Microparticles (MPs) are membrane vesicles which are released from normal and malignant cells following a process of budding and detachment from donor cells. MPs contain surface antigens, proteins and genetic material and serve as vectors of intercellular communication. MPs comprise the major source of systemic RNA including microRNA (miRNA), the aberrant expression of which appears to be associated with stage, progression and spread of many cancers. Our previous study showed that MPs carry both transcripts and miRNAs associated with the acquisition of multidrug resistance in cancer.
Herein, we expand on our previous finding and demonstrate that MPs carry the transcripts of the membrane vesiculation machinery (floppase and scramblase) as well as nucleic acids encoding the enzymes essential for microRNA biogenesis (Drosha, Dicer and Argonaute). We also demonstrate using microarray miRNA profiling analysis, the selective packaging of miRNAs (miR-1228*, miR-1246, miR-1308, miR-149*, miR-455-3p, miR-638 and miR-923) within the MP cargo upon release from the donor cells.
These miRNAs are present in both haematological and non-haematological cancer cells and are involved in pathways implicated in cancer pathogenesis, membrane vesiculation and cascades regulated by ABC transporters. Our recent findings reinforce our earlier reports that MP transfer 're-templates' recipient cells so as to reflect donor cell traits. We now demonstrate that this process is likely to occur via a process of selective packaging of nucleic acid species, including regulatory nucleic acids upon MP vesiculation. These findings have significant implications in understanding the cellular basis governing the intercellular acquisition and dominance of deleterious traits in cancers.
微粒（MPs）是细胞膜囊泡，在从供体细胞出芽和脱离的过程中从正常和恶性细胞释放。MPs 包含表面抗原、蛋白质和遗传物质，充当细胞间通讯的载体。MPs 构成包括 microRNA（miRNA）在内的系统 RNA 的主要来源，其异常表达似乎与许多癌症的分期、进展和扩散有关。我们之前的研究表明，MPs 携带与癌症获得多药耐药性相关的转录本和 miRNA。
在此，我们扩展了我们之前的发现，并证明 MPs 携带膜囊泡形成机制（floppase 和 scramblase）的转录本以及编码 miRNA 生物发生所必需的酶的核酸（Drosha、Dicer 和 Argonaute）。我们还使用微阵列 miRNA 谱分析证明，miRNA（miR-1228*、miR-1246、miR-1308、miR-149*、miR-455-3p、miR-638 和 miR-923）在供体细胞释放时选择性包装在 MP 货物中。
这些 miRNA 存在于血液系统和非血液系统癌细胞中，参与癌症发病机制、膜囊泡形成和 ABC 转运体调节的级联途径。我们最近的发现强化了我们之前的报告，即 MP 转移“重新模板化”受体细胞，以反映供体细胞特征。我们现在证明，这个过程可能是通过在 MP 囊泡化时选择性包装核酸物质，包括调节核酸来发生的。这些发现对理解控制癌症中有害特征的细胞间获得和优势的细胞基础具有重要意义。
