Similar Datasets
Project description:Tumor-associated macrophages are mainly polarized into the M2 phenotype, which remodels the tumor microenvironment and promotes tumor progression by secreting various cytokines. Herein, we reported that Yin Yang 1 (YY1) was highly expressed on tumor-infiltrated M2 macrophages in prostate cancer and was associated with poorer clinical outcomes. Using transgenic mice overexpressing YY1, we found that the tumor-promoting effects of oe-YY1 mice could be suppressed by macrophage depletion. Further in-vitro and in-vivo experiments using YY1 overexpressing and knocked down M2 macrophages demonstrated that YY1 induced M2 polarization and increased macrophages-induced prostate cancer progression by the IL-6/STAT3 pathway. Furthermore, YY1 promoted phase-separated condensates and upregulated IL-6 by modulating p300, p300 and CEBPB as a transcription complex. By conducting chromatin immunoprecipitation sequencing of M2 macrophages and monocytes, an M2-specific IL-6 enhancer associated with the YY1 complex was shown to upregulate IL-6 expression in M2 macrophages, and H3K27ac and YY1 signals significantly increased around this enhancer. In conclusion, YY1 complex promotes the M2 macrophages polarization and upregulates IL-6 in macrophages by inducing phase separation and a M2-specific enhancer, thereby increasing prostate cancer progression. These findings might lead to novel therapies targeting YY1 in prostate tumor-associated macrophages.
2023-04-01 | GSE200948 | GEO
Project description:Tumor-associated macrophages are mainly polarized into the M2 phenotype, which remodels the tumor microenvironment and promotes tumor progression by secreting various cytokines. Herein, we reported that Yin Yang 1 (YY1) was highly expressed on tumor-infiltrated M2 macrophages in prostate cancer and was associated with poorer clinical outcomes. Using transgenic mice overexpressing YY1, we found that the tumor-promoting effects of oe-YY1 mice could be suppressed by macrophage depletion. Further in-vitro and in-vivo experiments using YY1 overexpressing and knocked down M2 macrophages demonstrated that YY1 induced M2 polarization and increased macrophages-induced prostate cancer progression by the IL-6/STAT3 pathway. Furthermore, YY1 promoted phase-separated condensates and upregulated IL-6 by modulating p300, NF-κB and CEBPB as a transcription complex. By conducting chromatin immunoprecipitation sequencing of M2 macrophages and monocytes, an M2-specific IL-6 enhancer associated with the YY1 complex was shown to upregulate IL-6 expression in M2 macrophages, and H3K27ac and YY1 signals significantly increased around this enhancer. In conclusion, YY1 complex promotes the M2 macrophages polarization and upregulates IL-6 in macrophages by inducing phase separation and a M2-specific enhancer, thereby increasing prostate cancer progression. These findings might lead to novel therapies targeting YY1 in prostate tumor-associated macrophages.
2023-04-01 | GSE200947 | GEO
Project description:YY1 complex in tumor-associated macrophage promotes prostate cancer progression by upregulating IL-6
| PRJNA827698 | ENA
Project description:YY1 complex in tumor-associated macrophage promotes prostate cancer progression by upregulating IL-6 [RNA-seq]
| PRJNA827701 | ENA
Project description:YY1 complex in tumor-associated macrophage promotes prostate cancer progression by upregulating IL-6 [ChIP-seq]
| PRJNA827702 | ENA
Project description:Bone marrow macrophages (BMMs) share common progenitors with osteoclasts and are critical components of bone-tumor microenvironment; however, their function in prostate tumor growth in the skeleton has not been explored. BMMs are the major source of inflammatory factors and proteases, including cysteine protease cathepsin K (CTSK). In this study, utilizing mice deficient in CTSK, we demonstrate the critical involvement of this potent collagenase in tumor progression in bone. We present the evidence that tumor growth and progression in the bone are impaired in the absence of CTSK. Most importantly, we show for the first time that BMM-supplied CTSK may be involved in CCL2- and COX-2-driven pathways that contribute to tumor progression in bone. Together, our data unravel novel roles for CTSK in macrophage-regulated processes, and provide evidence for close interplay between inflammatory, osteolytic and tumor cell-driven events in the bone-tumor microenvironment.
| S-EPMC3913739 | biostudies-literature
Project description:Effective treatment of advanced prostate cancer persists as a significant clinical need as only 30% of patients with distant disease survive to 5 years after diagnosis. Targeting signaling and tumor cell-immune cell interactions in the tumor microenvironment has led to the development of powerful immunotherapeutic agents, however, the prostate tumor milieu remains impermeable to these strategies highlighting the need for novel therapeutic targets. In this study, we provide compelling evidence to support the role of the RON receptor tyrosine kinase as a major regulator of macrophages in the prostate tumor microenvironment. We show that loss of RON selectively in prostate epithelial cells leads to significantly reduced prostate tumor growth and metastasis and is associated with increased intratumor infiltration of macrophages. We further demonstrate that prostate epithelial RON loss induces transcriptional reprogramming of macrophages to support expression of classical M1 markers and suppress expression of alternative M2 markers. Interestingly, our results show epithelial RON activation drives upregulation of RON expression in macrophages as a positive feed-forward mechanism to support prostate tumor growth. Using 3D coculture assays, we provide additional evidence that epithelial RON expression coordinates interactions between prostate tumor cells and macrophages to promote macrophage-mediated tumor cell growth. Taken together, our results suggest that RON receptor signaling in prostate tumor cells directs the functions of macrophages in the prostate tumor microenvironment to promote prostate cancer. IMPLICATIONS: Epithelial RON is a novel immunotherapeutic target that is responsible for directing the macrophage antitumor immune response to support prostate tumor growth and progression.
| S-EPMC7415572 | biostudies-literature
Project description:The immune response facilitated by tumor-associated macrophages is a vital determinant of tumor progression. We identified differentially expressed genes between various macrophage phenotypes in the Gene Expression Omnibus, and used Kaplan-Meier Plotter to determine which of them altered the prognosis of esophageal carcinoma patients. Fibrinogen-like protein 2 (FGL2), an immunosuppressive factor in the tumor microenvironment of various cancers, was upregulated in M2 macrophages, and higher FGL2 expression was associated with poorer survival in esophageal carcinoma patients. Using the TIMER database, we found that FGL2 expression correlated positively with the levels of immune markers of infiltrating B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils and dendritic cells in esophageal carcinoma samples. Correlation analyses in cBioPortal revealed that the mRNA levels of FGL2 correlated strongly with those of interleukin 10, matrix metalloproteinase 9, C-C motif chemokine ligand 5, T-cell immunoglobulin mucin 3, interleukin 13, vascular cell adhesion molecule 1, macrophage colony-stimulating factor and fibroblast growth factor 7 in esophageal carcinoma tissues. The same cytokines were upregulated when esophageal squamous cell carcinoma cells were co-cultured with M2-like tumor-associated macrophages. Thus, by secreting FGL2, M2-like tumor-associated macrophages may create an immunosuppressive tumor microenvironment that induces the occurrence and progression of esophageal carcinoma.
| S-EPMC7880404 | biostudies-literature
Project description:The tumor-associated macrophage (TAM) is the most abundant group of immune cells in the tumor microenvironment (TME), which plays a critical role in the regulation of tumor progression and treatment resistance. Based on different polarization status, TAMs may also induce antitumor immune responses or immunosuppression. The present study identified JMJD6 (Jumonji domain-containing 6) as a novel modulator of TAM activation, the upregulation of which was associated with the immunosuppressive activities of TAMs. JMJD6 deficiency attenuated the growth of both Lewis lung carcinoma (LLC) tumors and B16F10 melanomas by reversing M2-like activation of macrophages, and sensitized tumors to immune checkpoint blockades (ICBs). Moreover, the JMJD6-induced inhibition of M2 polarization was potentially mediated by the STAT3/IL-10 signaling. These findings highlight the regulatory activities of JMJD6 in TAM polarization, and the therapeutic potential of JMJD6/STAT3/IL-10 axis blockades to enhance the efficacy of ICBs in cancer treatment.
| S-EPMC10491492 | biostudies-literature
Project description:BackgroundForkhead box S1 (FOXS1) is a member of the forkhead box (FOX) transcriptional factor superfamily. The biological roles and underlying regulatory mechanism of FOXS1 in CRC remain unclear.MethodsBioinformatics analysis, Western blotting, real-time PCR, and immunohistochemistry (IHC) were used to detect the expression FOXS1 in CRC. MTT assay, transwell assay, human umbilical vein endothelial cell tube formation assay, and chicken chorioallantoic membrane assay were performed to investigate the effects of FOXS1 on proliferation, invasion, and angiogenesis. Additionally, tumor formation assay and orthotopic implantation assay were used to investigate the effects of FOXS1 on tumor growth and metastasis in vivo. Furthermore, gene set enrichment analysis (GSEA) was used to analyze the correlation between FOXS1 and EMT or angiogenesis. The correlation between FOXS1 and CXCL8 expression was analyzed in clinical CRC samples using IHC.ResultsThe results showed that FOXS1 expression was upregulated in CRC tissues compared with adjacent normal intestine tissues. A high FOXS1 expression is positively correlated with poor survival. FOXS1 promoted the malignant behavior of CRC cancer cells in vitro, including proliferation, invasion, and angiogenesis. In addition, FOXS1 promoted tumor growth and metastasis in nude mice. Mechanistically, FOXS1 upregulated the expression of C-X-C motif chemokine ligand 8 (CXCL8) at the transcriptional level. Knockdown of CXCL8 blocked FOXS1 induced the enhancement of the EMT and angiogenesis. GSEAs in public CRC datasets revealed strong correlations between FOXS1 expression and EMT marker and angiogenesis markers. IHC showed that FOXS1 expression was positively correlated with CXCL8 expression and CD31 expression in clinical CRC samples.ConclusionThe results suggest that FOXS1 promotes angiogenesis and metastasis by upregulating CXCL8 in CRC. Interference with the FOXS1/CXCL8 axis may serve as a potential therapeutic target for the treatment of metastatic CRC.
| S-EPMC9309265 | biostudies-literature