OSM/OSMR相互作用介导肿瘤相关巨噬细胞促胶质母细胞瘤侵袭的表型与机制

肿瘤相关巨噬细胞（TAM）在促胶质母细胞瘤（GBM）侵袭中发挥重要作用，但机制不明。我们前期发现，抑瘤素M受体（OSMR）在GBM中高表达。预实验结果表明，配体OSM主要来源于TAM；敲低OSMR可减弱GBM细胞的侵袭力，引起间质型基因的下调和前神经元型基因的上调；以及JAK/STAT与YAP/TAZ信号在高表达OSMR的GBM中显著富集。基于此，我们提出“TAM可能通过分泌OSM，作用于GBM细胞上的OSMR，进而激活JAK/STAT与YAP/TAZ信号，诱导前神经元表型向间质表型转化而促进侵袭”的科学假说。本研究拟在分析OSM和OSMR的表达与GBM预后的基础上，通过体内外实验和组学分析探讨OSM/OSMR相互作用介导TAM促GBM侵袭的功能表型与分子机制，为进一步认识TAM调控GBM侵袭机制、评估GBM预后和研发干预GBM侵袭的治疗策略提供理论与实验依据。

Tumor-associated macrophage (TAM) plays an important role in promoting glioblastoma (GBM) invasion, but the underlying mechanism remains elusive. We previously found that Oncostatin M receptor (OSMR) was highly expressed in GBM. The preliminary experiments were conducted and showed that the ligand OSM in GBM was mainly secreted by TAM. Knockdown of OSMR in GBM cells inhibited the invasive ability, downregulated the mesenchymal genes, and upregulated the proneural genes. Besides, JAK/STAT pathway and YAP/TAZ signaling were enriched in GBM highly expressed OSMR via gene set enrichment analysis. Therefore, we propose that interaction between OSM from TAMs and OSMR on GBM cells may promote GBM invasion by inducing proneural-mesenchymal transition via JAK/STAT pathway and YAP/TAZ signaling. We plan to evaluate the prognostic value of OSM and OSMR expression on GBM patients, and then explore the role and the underlying mechanism of interaction between OSMR on GBM cells and OSM from TAMs on GBM invasion through in vivo and in vitro experiments, transcriptional analysis, etc. Our results may provide the essential experimental evidence and theoretical basis for further understanding of the mechanism underlying the enhanced GBM invasion by TAM, for the prognosis prediction of GBM, and for the development of therapeutic strategy targeting GBM invasion.