Transmissible ER stress between macrophage and tumor cells configures tumor microenvironment

ABSTRACT: Purpose: To investigate the critical role ER stress exhibit in cellular crosstalk between tumor cells and macrophages in the tumor microenvironment. We performed the two different polarized macrophages under ER stress and harvested the ER-stressed conditioned media. To figure out how two macrophage polarities generated conditioned media impact LLC tumor cells diversely, we use RNA-sequencing (RNA-seq) strategies to profile the deep-sequencing research and find the potential molecular mechanisms during the ER stress transmission from macrophages to tumor cells. The major differential influences the two macrophages proceeded were attribute to macrophages polarization characteristics, which instruct us to study the two polarized macrophages. Hence, we also performed RNA-sequencing during in vitro stimulation of ER stress inducer Tm in two polarized bone marrow derived macrophages. Methods: After different treatment, LLC tumor cells mRNA was extracted and LLC tumor cells transcriptome profiles were generated by deep sequencing, using Illumina. Under ER stress, the different polarized macrophages transcriptome profiles were also generated by deep sequencing, using Illumina. Results: Macrophages displayed different polarization characteristics could respond to ER stress differentially. Notably, GM-BMDMs were more susceptible to ER stress and facilitated the induction of proinflammatory signals, and M-BMDMs facilitate tumor growth, process, and metastasis. LLC cells exhibit different gene expression profiles in response to transferred ER stress from two polarized macrophage populations. Tumor cells that received transmissible ER stress from M2 macrophages has potential to facilitate the tumor survival, while transmissible ER stress from M1 macrophages could lead to more acute cell death and inflammation. Conclusion: Our study revealed that tumor cells could receive the transmissible ER stress from distinct macrophage populations with different extents of ER stress activation in the tumor microenvironment. The proinflammatory M1-like macrophages respond to ER stress more potently and transmit stronger ER stress to tumor cells. By analyzing the secreted components of two ER stressed macrophage populations, we identified that S100A8 and S100A9, which are dominantly secreted by M1-like macrophages, could lead to significant recipient tumor cell death in synergy with transferred ER stress.

ORGANISM(S): Mus musculus

PROVIDER: GSE193669 | GEO | 2022/12/22

REPOSITORIES: GEO