Exosomes/Microvesicles: Novel Mechanisms of Cell-Cell Communication

 描述（由申请人提供）：请求支持由Richard A. Cerione和Xandra O.布雷克菲尔德会议将于2016年6月19日至22日在科罗拉多的基斯通举行。在细胞生物学和制药/生物技术领域，一个令人兴奋的新兴领域涉及膜封闭的信息包（通常称为细胞外囊泡）的释放和随后的摄取。这些非传统的囊泡含有一系列有效的货物，包括数百种蛋白质，如生长因子和受体，代谢酶，转录因子和各种RNA转录物以及DNA。细胞外囊泡的尺寸范围从50 nm到1微米，并且包含异质集，包括似乎通过不同机制产生的外泌体和微囊泡。细胞外囊泡被认为是细胞间通讯的一种手段，并有助于许多疾病状态，包括癌症和神经变性，从而为治疗干预提供新的靶点，并为诊断生物标志物提供新的可能性。然而，一些重要的问题需要回答：是什么调节线索，决定内容和释放这些囊泡从“供体”细胞？有多少种不同类型的细胞外囊泡，它们在不同的细胞类型中是否存在差异？囊泡进入“受体细胞”是否有特定的摄取机制，以及这些细胞中的货物是否有功能？现在是时候召开一次Keystone研讨会了，该会议涵盖了这一令人兴奋的领域，旨在将来自细胞生物学和生物医学界的研究人员聚集在一起，展示他们关于细胞外囊泡生物发生的最新发现，它们如何脱落并停靠在靶细胞上，以及它们功能的生物学和疾病后果。鉴于微泡/外泌体功能与癌症进展之间的联系数量，本次会议的重点与NCI特别相关。例如，细胞外囊泡涉及原发性肿瘤部位的癌细胞与其直接微环境之间的通讯，以及在肿瘤集落形成的继发部位产生转移前小生境，以及肿瘤血管生成。此外，这些囊泡在组织液中是稳定的，并且具有用作生物标志物的潜力，其想法是来自不同类型癌细胞的微囊泡/外泌体将含有一些对这些细胞特异性的货物。因此，微泡/外来体为鉴定新的治疗性抗癌靶点和诊断标志物提供了潜在的丰富领域。

 DESCRIPTION (provided by applicant): Support is requested for a Keystone Symposia meeting entitled Exosomes/Microvesicles: Novel Mechanisms of Cell-Cell Communication, organized by Richard A. Cerione and Xandra O. Breakefield. The meeting will be held in Keystone, Colorado from June 19-22, 2016. An emerging area of great excitement in the cell biology and pharmaceutical/biotech communities involves the release and subsequent uptake of membrane-enclosed packets of information, often referred to as extracellular vesicles. These non-traditional vesicles contain a potent array of cargo, including hundreds of proteins such as growth factors and receptors, metabolic enzymes, transcription factors and a large variety of RNA transcripts as well as DNA. Extracellular vesicles span a range of sizes from 50 nm to 1 micron and comprise a heterogenous set, including exosomes and microvesicles that appear to be generated through distinct mechanisms. Extracellular vesicles are thought to serve as a means of cell-to-cell communication and contribute to a number of disease states, including cancer and neurodegeneration, thus offering new targets for therapeutic intervention and novel possibilities for diagnostic biomarkers. However, a number of important questions need to be answered: What are the regulatory cues that determine content and release of these vesicles from "donor" cells? How many different types of extracellular vesicles are there and do they vary among cell types? Are there specific uptake mechanisms of vesicles into "recipient cells" and is the cargo functional in these cells? The time is right for a Keystone Symposia meeting that covers this exciting area and aims to bring together investigators from the cell biology and biomedical communities to present their newest findings concerning the biogenesis of extracellular vesicles, how they are shed and dock onto target cells, and the biological and disease consequences of their functions. This meeting's focus is particularly relevant to NCI given the number of connections between microvesicle/exosome function and cancer progression. For example, extracellular vesicles have been implicated in the communication between cancer cells at a primary tumor site and their immediate microenvironment, as well as in the creation of the pre-metastatic niche at secondary sites of tumor colony formation, and in tumor angiogenesis. Moreover, these vesicles are stable in tissue fluids and have the potential to serve as biomarkers, with the idea being that microvesicles/exosomes from different types of cancer cells will contain some cargo specific to those cells. Thus, microvesicles/ exosomes offer a potentially rich area for the identification of new therapeutic anti-cancer targets and diagnosti markers