黑色素瘤细胞来源微颗粒介导巨噬细胞释放IL-1β：肿瘤转移前微环境形成的新机制。

Tumor pre-metastatic niche is considered to be a key segment of metastatic tumor formation. So far, the concrete mechanism of tumor pre-metastatic niche formation is not clear. Microparticle is a kind of small vesicle which is containing the cellular contents wrapped by cell membrane and could release to the extracellular space, which is also utilized for cell-cell information transfer. In the process of tumor development, apoptosis or stimulated tumor cells are able to produce and release microparticles. Applicants’ preliminary work found that melanoma cell-derived microparticle (T-MP) promoted lung metastasis of melanoma and T-MP could induce IL-1β expression secreted by macrophages in vitro. Based on the above, this project is intended to study whether englufed T-MP induces lung macrophages IL-1β secretion, and mediates the accumulation of myeloid cells, and last initiates the formation of lung tumor pre-metastatic niche. In addition, this project will also elucidate the mechanism how T-MP mediates high expression of IL-1β derived by macrophage at the molecular level. This project is expected to elucidate the mechanism of tumor pre-metastatic niche formation from a new perspective, and to provide new ideas and potential targets for the prevention and treatment of tumor metastasis.

肿瘤转移前微环境（pre-metastatic niche）被认为是转移肿瘤形成的关键环节。迄今为止，肿瘤转移前微环境形成的具体机制并不清楚。微颗粒是由细胞膜包裹细胞内容物、并释放到细胞外的一类可以在细胞间进行信息传递的囊状小泡。在肿瘤发展过程中，凋亡或者受刺激的肿瘤细胞均能够产生并释放微颗粒。申请人前期工作发现黑色素瘤细胞来源的微颗粒（T-MP）可以促进黑色素瘤的肺转移，并在体外发现T-MP可以诱导巨噬细胞IL-1β的表达。基于此，本项目拟对T-MP是否在体内被肺部巨噬细胞吞噬，并介导其IL-1β的分泌，从而诱导髓系细胞向肺部迁移聚集，乃至形成肿瘤转移前微环境进行研究。另外，本项目还将从分子层面，分析T-MP如何介导巨噬细胞上调IL-1β的表达。本项目的完成，有望从一个全新角度阐明肿瘤转移前微环境的相关机理，为肿瘤转移的防治提供新的思路和潜在靶点。

肿瘤转移前微环境（pre-metastatic niche）被认为是转移肿瘤形成的关键环节。迄今为止，肿瘤转移前微环境形成的具体机制并不清楚。微颗粒是由细胞膜包裹细胞内容物、并释放到细胞外的一类可以在细胞间进行信息传递的囊状小泡。在肿瘤发展过程中，凋亡或者受刺激的肿瘤细胞均能够产生并释放微颗粒。申请人前期工作发现黑色素瘤细胞来源的微颗粒（T-MP）可以促进黑色素瘤的肺转移，并在体外发现T-MP可以诱导巨噬细胞IL-1β的表达。基于此，本项目拟对T-MP是否在体内被肺部巨噬细胞吞噬，并介导其IL-1β的分泌，从而诱导髓系细胞向肺部迁移聚集，乃至形成肿瘤转移前微环境进行研究。另外，本项目还将从分子层面，分析T-MP如何介导巨噬细胞上调IL-1β的表达。本项目的完成，有望从一个全新角度阐明肿瘤转移前微环境的相关机理，为肿瘤转移的防治提供新的思路和潜在靶点。