S100A9 from tumor-associated macrophage enhances cancer stem cell-like properties of hepatocellular carcinoma
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PROVIDER: PRJNA666559 | ENA |
REPOSITORIES: ENA
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Project description:Tumor-associated macrophages (TAMs) are crucial components of the tumor microenvironment (TME). They play vital roles in hepatocellular carcinoma (HCC) progression. However, the interactions between TAMs and HCC cells have not been fully characterized. In this study, TAMs were induced using human monocytic cell line THP-1 cells in vitro to investigate their functions in HCC progression. S100 calcium binding protein A9 (S100A9), an inflammatory microenvironment-related secreted protein, was identified to be significantly upregulated in TAMs. S100A9 expression in tumor tissues was associated with poor survival of HCC patients. It could enhance the stem cell-like properties of HepG2 and MHCC-97H cells by activating nuclear factor-kappa B (NF-κB) signaling pathway through advanced glycosylation end-product specific receptor (AGER) in a Ca2+-dependent manner. Furthermore, we found that, after treatment with S100A9, HepG2 and MHCC-97H cells recruited more macrophages via chemokine (C-C Motif) ligand 2 (CCL2), which suggests a positive feedback between TAMs and HCC cells. Taken together, our findings reveal that TAMs could upregulate secreted protein S100A9 and enhance the stem cell-like properties of HCC cells, and provide a potential therapeutic target for combating HCC.
2020-10-23 | GSE158792 | GEO
Project description:S100A9 from tumor-associated macrophage enhances cancer stem cell-like properties of hepatocellular carcinoma (RNA-Seq)
| PRJNA668158 | ENA
Project description:Tumor-associated macrophages (TAMs) are crucial components of the tumor microenvironment (TME). They play vital roles in hepatocellular carcinoma (HCC) progression. However, the interactions between TAMs and HCC cells have not been fully characterized. In this study, TAMs were induced using human monocytic cell line THP-1 cells in vitro to investigate their functions in HCC progression. S100 calcium binding protein A9 (S100A9), an inflammatory microenvironment-related secreted protein, was identified to be significantly upregulated in TAMs. S100A9 expression in tumor tissues was associated with poor survival of HCC patients. It could enhance the stem cell-like properties of HepG2 and MHCC-97H cells by activating nuclear factor-kappa B (NF-κB) signaling pathway through advanced glycosylation end-product specific receptor (AGER) in a Ca2+-dependent manner. Furthermore, we found that, after treatment with S100A9, HepG2 and MHCC-97H cells recruited more macrophages infiltration via chemokine (C-C Motif) ligand 2 (CCL2), which suggests a positive feedback between TAMs and HCC cells. Taken together, our findings reveal that TAMs could upregulate S100A9 and enhance the stem cell-like properties of HCC cells, and provide a potential therapeutic target for combating HCC.
2020-10-23 | GSE159264 | GEO
Project description:Mycobacterium infection gives rise to granulomas predominantly composed of inflammatory M1-like macrophages, with bacteria-permissive M2 macrophages also detected in deep granulomas. Our histological analysis of Mycobacterium bovis bacillus Calmette-Guerin-elicited granulomas in guinea pigs revealed that S100A9-expressing neutrophils bordered a unique M2 niche within the inner circle of concentrically multilayered granulomas. We evaluated the effect of S100A9 on macrophage M2 polarization based on guinea pig studies. S100A9-deficient mouse neutrophils abrogated M2 polarization, which was critically dependent on COX-2 signaling in neutrophils. Mechanistic evidence suggested that nuclear S100A9 interacts with C/EBPβ, which cooperatively activates the Cox-2 promoter and amplifies prostaglandin E2 production, followed by M2 polarization in proximal macrophages. Since the M2 populations in guinea pig granulomas were abolished via treatment with celecoxib, a selective COX-2 inhibitor, we propose the S100A9/Cox-2 axis as a major pathway driving M2 niche formation in granulomas.
2023-03-01 | GSE162991 | GEO
Project description:Neutrophil S100A9 supports M2 macrophage niche formation in granulomas
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Project description:Hepatocellular carcinoma (HCC) is a major cause of cancer-related mortality worldwide, largely due to its complex and immunosuppressive tumor immune microenvironment (TIME), which significantly impairs the efficacy of conventional therapies and immune checkpoint blockade (ICB). This study investigates the role of C-C motif chemokine ligand 3 (CCL3) in modulating the HCC TIME, focusing on its impact on immune cell recruitment, macrophage-mediated antigen presentation, and the overall antitumor immune response. We analyzed CCL3 expression in human HCC samples and examined its correlation with inflammatory gene signatures and immune cell infiltration. Using high-dimensional single-cell RNA sequencing (scRNA-seq), multiparameter flow cytometry, and multiplex immunofluorescence, we elucidated how CCL3 influences macrophage functionality and T cell activation. In preclinical HCC models and ex vivo tumor fragment assays, we explored the mechanisms by which CCL3 affects macrophage function and its broader implications for antitumor immunity. Our findings reveal that CCL3 effectively recruits immune cells to the HCC TIME, promotes the formation of tertiary lymphoid structures, and enhances macrophage-mediated antigen phagocytosis and presentation, leading to improved T cell effector functions and cytotoxic activity. This research underscores the critical role of CCL3 in reshaping the HCC TIME to enhance antitumor immunity and suggests that targeting CCL3 could be a promising strategy to improve the efficacy of immunotherapy in liver cancer.
2025-03-03 | GSE277065 | GEO
Project description:Hepatocellular carcinoma (HCC) is a major cause of cancer-related mortality worldwide, largely due to its complex and immunosuppressive tumor immune microenvironment (TIME), which significantly impairs the efficacy of conventional therapies and immune checkpoint blockade (ICB). This study investigates the role of C-C motif chemokine ligand 3 (CCL3) in modulating the HCC TIME, focusing on its impact on immune cell recruitment, macrophage-mediated antigen presentation, and the overall antitumor immune response. We analyzed CCL3 expression in human HCC samples and examined its correlation with inflammatory gene signatures and immune cell infiltration. Using high-dimensional single-cell RNA sequencing (scRNA-seq), multiparameter flow cytometry, and multiplex immunofluorescence, we elucidated how CCL3 influences macrophage functionality and T cell activation. In preclinical HCC models and ex vivo tumor fragment assays, we explored the mechanisms by which CCL3 affects macrophage function and its broader implications for antitumor immunity. Our findings reveal that CCL3 effectively recruits immune cells to the HCC TIME, promotes the formation of tertiary lymphoid structures, and enhances macrophage-mediated antigen phagocytosis and presentation, leading to improved T cell effector functions and cytotoxic activity. This research underscores the critical role of CCL3 in reshaping the HCC TIME to enhance antitumor immunity and suggests that targeting CCL3 could be a promising strategy to improve the efficacy of immunotherapy in liver cancer.
2025-03-05 | GSE277066 | GEO
Project description:In order to explore how S100A8 and S100A9 may participate in the kidney stone formation, we used recombinant S100A8, recombinant S100A9, or recombinant S100A8/S100A9 heterodimer to culture the HK-2 cells and then sequenced total cellular mRNAS.
2024-11-06 | GSE265848 | GEO
Project description:We identified the alarmin S100A9 as a novel intracellular antiretroviral factor expressed in human monocyte-derived and skin-derived Langerhans cells (LC). The expression of S100A9 is significantly upregulated by the transforming growth factor beta in human monocyte-derived cells. We showed that S100A9 intracellular expression is decreased upon maturation and inversely correlated with an enhanced inversely correlates with the maturation level of LC and susceptibilityility to HIV-1 infection of LC. Furthermore, silencing of S100A9 in primary human LC relieves HIV-1 restriction while ectopic expression of S100A9 in various cell lines established an intrinsic resistance to both HIV-1 and MMLV infection by acting on reverse transcription. Mechanistically, the intracellular expression of S100A9 alters viral capsid uncoating and reverse transcription in a distal manner. Also, S100A9 demonstrates potent inhibitory effect against HIV-1 and MMLV reverse transcriptase (RTase) activity in-vitro in a divalent cation-dependent context. Our findings uncover an unexpected intracellular antiretroviral function of the human alarmin S100A9 and highlight a novel crosstalk betweenregulating antiretroviral immunity in Langerhans cells
2021-05-06 | GSE173939 | GEO