Imaging endogenously produced tumor derived micro vesicles

描述（由申请人提供）：尽管肿瘤细胞内源性基因突变是肿瘤进展的主要驱动力，但最近的研究表明，肿瘤的生长也受到肿瘤细胞与其宿主的外源性相互作用的深刻调节。具体来说，癌症的生长可能受到各种免疫细胞类型的控制，这些免疫细胞抑制或促进肿瘤的进展和转移，并可能部分由癌细胞直接调节。该应用程序致力于使用新技术来研究癌细胞如何与体内远处的细胞交流，以及这种交流是否以及如何影响癌症的生长。我们将专门研究肿瘤来源的微泡（tMVs）作为肿瘤细胞和远离肿瘤基质的免疫细胞之间的信息传送带。tmv携带肿瘤来源的物质（蛋白质，mrna），在保持其内容物未降解和未稀释的情况下在体内短距离或长距离移动，并可能与远程组织中的不同宿主细胞类型相互作用（并通过扩展控制）；然而，tmv的生物学功能在很大程度上仍然未知。在这一领域取得进展的一个关键障碍是我们有限的能力

DESCRIPTION (provided by applicant): Although tumor cell endogenous genetic mutations are major driving forces of tumor progression, recent work has established that cancer growth is also profoundly modulated by tumor cell exogenous interactions with its host. Specifically, cancer outgrowth may be controlled by various immune cell types, which either suppress or promote tumor progression and metastasis, and may be regulated in part by cancer cells directly. This application is dedicated to use new technology to investigate how cancer cells communicate with distant cells in the body, and whether and how this communication affects cancer growth. We will specifically study tumor-derived microvesicles (tMVs) as conveyors of information between tumor cells and immune cells that reside away from the tumor stroma. tMVs carry tumor-derived material (proteins, mRNAs), travel short or long distances in the body while keeping their contents undegraded and undiluted, and may interact with (and by extension control) different host cell types in remote tissues; however, the biological functions of tMVs remain largely unknown. A critical barrier to progress in the field has been our limited ability to understand the impact of tMVs that are produced endogenously in vivo. Indeed, the body of work on tMV-immune cell interactions so far has required the use of in vitro-manipulated tMVs, which may not allow one to fully recapitulate the features of endogenously produced particles. At present, the precise location and identity of immune cells interacting with endogenously produced tMVs is unknown, as is the impact of such interactions on tumor progression. To shift current experimental research approaches to study tMVs directly in vivo, this 2-year project will combine: 1) molecular imaging and 2) new genetic approaches to track endogenously produced tMVs and their targets at different resolutions and scales (organismal, cellular and molecular). Findings from this research should not only validate important new tools to study tumor cell-host cell interactions in many different experimental settings, but also deepen our understanding of tMVs and ultimately open up new avenues for anti-cancer therapy.