Exogenous HMGB1 promotes pancreatic cancer progression by supporting the crosstalk between tumor and myeloid-derived suppressor cell DOI Creative Commons
Faming Wang, Wei Wei,

Tao San

и другие.

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Янв. 25, 2024

Abstract Background The main reasons pancreatic cancer (PC) is difficult to treat are high tissue fibrosis and a strong immunosuppressive microenvironment. Therefore, it necessary elucidate the cause mechanism of tumour microenvironment formation. High-mobility group Box 1 (HMGB1) highly conserved nuclear protein that widely distributed in mammalian cells plays an important role tumours. However, functions mechanisms HMGB1 PC remain controversial. Here, we report novel for formation immune Methods In this study, expression level samples was detected patients TCGA database. relative serum tissues evaluated by enzyme-linked immunosorbent assay (ELISA). Flow cytometry used detect infiltration myeloid-derived suppressor (MDSCs) regulatory T tumours from xenograft mouse models treated with HMGB1. Vascular density cytokine levels were measured immunohistochemistry (IHC). HMGB1-associated differentially expressed genes GEPIA database analyse GO terms KEGG pathways. Subsequently, related proteins Western blotting. Results higher than normal tissues. High predict poor overall survival patients, suggesting its potential clinical significance prognosis. model results show significantly promotes growth. We further found CD69 + CD8 markedly decreased HMGB1-treated mice. Furthermore, after treatment HMGB1, into increased. IHC showed promoted intracellular inflammatory factors neovascularization. Mechanistically, indicated enhanced CXCL2 chemokines attract MDSCs upregulates through MAPK pathway. Conclusion conclusion, unexpected metastasis promoting microvessel mediated pathway recruit MDSC aggregation, which turn creates Thus, may be mediator therapeutic target regulating progression.

Язык: Английский

Macrophages-derived high mobility group box-1 protein induces endothelial progenitor cells pyroptosis DOI Creative Commons

Menghao Zeng,

Gui-Bin Liang, Fangfang Yuan

и другие.

iScience, Год журнала: 2024, Номер 27(10), С. 110996 - 110996

Опубликована: Сен. 20, 2024

Язык: Английский

Процитировано

1
Adverse Crosstalk Between Extracellular Matrix Remodeling and Ferroptosis in Basal Breast Cancer DOI Open Access
Christophe Desterke, Emma Cosialls, Yao Xiang

и другие.

Опубликована: Июнь 8, 2023

(1) Background: Breast cancer is a frequent heterogeneous disorder diagnosed in woman and high cause of mortality them reason to rapid metastasis disease recurrence. Ferroptosis can inhibit breast cell growth, improve the sensitivity chemotherapy radiotherapy distant metastases so potentially acts on tumor micro-environment; (2) Methods: Ferroptosis/Extracellular matrix remodeling literature text-mining results were integrated transcriptome cohort according their relapse free survival (DRFS) under adjuvant therapy (anthracyclin+taxanes) also MDA-MB-231 functional experiments with ferroptosis activations (GSE173905); (3) Results: identified 910 associated genes at list 10 articles. Univariate Cox analyses censored (GSE25066) selected 252 individual significant 171 found an adverse expression. Functional enrichment these predicted basal signatures. By some shared citations domain ECM such as: TNF, IL6, SET, CDKN2A, EGFR, HMGB1, KRAS, MET, LCN2, HIF1A, TLR4. A molecular score based expression eleven was predictive worst prognosis univariate level: subtype, short DRFS, grade values 3 4, estrogen progesterone receptors negative nodal stages 2 3. This gene signature validated as regulated by inductors (erastin RSL3) triple cellular model MDA-MB-231.; (4) Conclusions: Crosstalk between remodeling-Ferroptosis functionalities allowed define which have been characterized independent parameter patients. Gene this be erastin/RSL3 activators. could promising evaluate impact target therapies cancer.

Язык: Английский

Процитировано

2
Serum Hmgb-1 Released by Ferroptosis and Necroptosis as a Novel Potential Biomarker for Systemic Lupus Erythematosus DOI

Guowang Zhao,

Hongtao Lei,

Nuobing Ruan

и другие.

Опубликована: Янв. 1, 2024

Язык: Английский

Процитировано

0
Targeting BMAL1 reverse drug resistance of acute myeloid leukemia cells and promoting ferroptosis through HMGB1-GPX4 signaling pathway DOI Creative Commons
Hong Zheng, Ting Wu, Zhi Lin

и другие.

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Янв. 23, 2024

Abstract Purpose Acute myeloid leukemia (AML) is a refractory hematologic malignancy that poses serious threat to human health. Exploring alternative therapeutic strategies capable of inducing modes cell death, such as ferroptosis, holds great promise viable and effective intervention. Methods We analyzed online database data collected clinical samples verify the expression function BMAL1 in AML. conducted experiments on AML proliferation, cycle, chemotherapy resistance by overexpressing/knocking down using assays MDA detection BODIPY 581/591 C11 staining. validated transcriptional regulation HMGB1 through ChIP assay, luciferase RNA level detection, western blotting. Finally, we confirmed results our at animal level. Results up-regulation an observed phenomenon patients. Furthermore, there existed strong correlation between elevated levels inferior prognosis individuals with found knocking inhibited growth blocking cycle. Conversely, overexpressing promoted proliferation. Moreover, research revealed ferroptosis cells BMAL1-HMGB1-GPX4 pathway. can enhance efficacy certain first-line cancer drugs, including venetoclax, dasatinib, sorafenib. Conclusion Our suggest plays crucial regulatory role drug resistance, ferroptosis. could be potential important target for

Язык: Английский

Процитировано

0
Exogenous HMGB1 promotes pancreatic cancer progression by supporting the crosstalk between tumor and myeloid-derived suppressor cell DOI Creative Commons
Faming Wang, Wei Wei,

Tao San

и другие.

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Янв. 25, 2024

Abstract Background The main reasons pancreatic cancer (PC) is difficult to treat are high tissue fibrosis and a strong immunosuppressive microenvironment. Therefore, it necessary elucidate the cause mechanism of tumour microenvironment formation. High-mobility group Box 1 (HMGB1) highly conserved nuclear protein that widely distributed in mammalian cells plays an important role tumours. However, functions mechanisms HMGB1 PC remain controversial. Here, we report novel for formation immune Methods In this study, expression level samples was detected patients TCGA database. relative serum tissues evaluated by enzyme-linked immunosorbent assay (ELISA). Flow cytometry used detect infiltration myeloid-derived suppressor (MDSCs) regulatory T tumours from xenograft mouse models treated with HMGB1. Vascular density cytokine levels were measured immunohistochemistry (IHC). HMGB1-associated differentially expressed genes GEPIA database analyse GO terms KEGG pathways. Subsequently, related proteins Western blotting. Results higher than normal tissues. High predict poor overall survival patients, suggesting its potential clinical significance prognosis. model results show significantly promotes growth. We further found CD69 + CD8 markedly decreased HMGB1-treated mice. Furthermore, after treatment HMGB1, into increased. IHC showed promoted intracellular inflammatory factors neovascularization. Mechanistically, indicated enhanced CXCL2 chemokines attract MDSCs upregulates through MAPK pathway. Conclusion conclusion, unexpected metastasis promoting microvessel mediated pathway recruit MDSC aggregation, which turn creates Thus, may be mediator therapeutic target regulating progression.

Язык: Английский

Процитировано

0