The epithelial-mesenchymal transition of glioma cells promotes tissue factor expression via the miR200a/ZEB1 axis

SummaryAn experimental model incorporating cultured endothelial cells (EC) was used to study the "factor VIII bypassing" activity of prothrombin complex concentrates (PCC), a property exploited in the treatment of hemophiliacs with alloantibodies to factor VIII. Two PCC preparations were ineffective as stimuli of tissue factor expression by EC. However, incubation with a combination of PCC plus endotoxin (lipopolysaccharide, LPS) or tumor necrosis factor (TNF) induced much greater tissue factor expression than was seen in response to either substance alone. PCC expressed an additional direct procoagulant activity at the EC surface, which could not be attributed to either thrombin or factor Xa, and which was diminished by an anti-tissue factor antibody. Therefore factor VIIa, which was detectable in both PCC preparations, likely provided this additional direct procoagulant activity at the EC surface. We also excluded the possibility that coagulation proteases contained in or generated in the presence of PCC are protected from inactivation by AT III. Therefore, PCC can indirectly bypass factor VIII by enhancing induced endothelial tissue factor expression, and also possess direct procoagulant activity, probably mediated by factor VIIa.

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Faculty Opinions recommendation of Extracellular histones induce tissue factor expression in vascular endothelial cells via TLR and activation of NF-κB and AP-1.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725858467.793540030 ◽

2017 ◽

Author(s):

Cheng-Hock Toh

Keyword(s):

Endothelial Cells ◽

Tissue Factor ◽

Vascular Endothelial Cells ◽

Vascular Endothelial ◽

Tissue Factor Expression ◽

Factor Expression ◽

Extracellular Histones

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Tissue factor expression and tumor‐infiltrating T lymphocytes in ovarian carcinomas and their association with venous thromboembolism

Pathology International ◽

10.1111/pin.13074 ◽

2021 ◽

Author(s):

Toshihiro Gi ◽

Atsushi Yamashita ◽

Murasaki Aman ◽

Aya Kuwahara ◽

Yujiro Asada ◽

...

Keyword(s):

Venous Thromboembolism ◽

T Lymphocytes ◽

Tissue Factor ◽

Tissue Factor Expression ◽

Ovarian Carcinomas ◽

Factor Expression

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Tissue factor promotes airway pathological features through epithelial-mesenchymal transition of bronchial epithelial cells in mice with house dust mite-induced asthma

International Immunopharmacology ◽

10.1016/j.intimp.2021.107690 ◽

2021 ◽

Vol 97 ◽

pp. 107690

Author(s):

Junwei Zhao ◽

Tianci Jiang ◽

Pengfei Li ◽

Lingling Dai ◽

Guang Shi ◽

...

Keyword(s):

Epithelial Cells ◽

Tissue Factor ◽

House Dust ◽

House Dust Mite ◽

Epithelial Mesenchymal Transition ◽

Bronchial Epithelial Cells ◽

Pathological Features ◽

Bronchial Epithelial ◽

Mesenchymal Transition ◽

Dust Mite

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CD90low glioma-associated mesenchymal stromal/stem cells promote temozolomide resistance by activating FOXS1-mediated epithelial-mesenchymal transition in glioma cells

Stem Cell Research & Therapy ◽

10.1186/s13287-021-02458-8 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Bing-zhou Xue ◽

Wei Xiang ◽

Qing Zhang ◽

Hao-fei Wang ◽

Yu-jie Zhou ◽

...

Keyword(s):

Stem Cells ◽

Cell Line ◽

Epithelial Mesenchymal Transition ◽

Chemotherapy Resistance ◽

Glioma Cells ◽

Conditioned Media ◽

Cell Counting ◽

Mesenchymal Transition ◽

Mesenchymal Transformation ◽

Stromal Stem Cells

Abstract Background The tumour microenvironment contributes to chemotherapy resistance in gliomas, and glioma-associated mesenchymal stromal/stem cells (gaMSCs) are important stromal cell components that play multiple roles in tumour progression. However, whether gaMSCs affect chemotherapy resistance to the first-line agent temozolomide (TMZ) remains unclear. Herein, we explored the effect and mechanism of gaMSCs on resistance to TMZ in glioma cells. Methods Human glioma cells (cell line U87MG and primary glioblastoma cell line GBM-1) were cultured in conditioned media of gaMSCs and further treated with TMZ. The proliferation, apoptosis and migration of glioma cells were detected by Cell Counting Kit-8 (CCK-8), flow cytometry and wound-healing assays. The expression of FOXS1 in glioma cells was analysed by gene microarray, PCR and Western blotting. Then, FOXS1 expression in glioma cells was up- and downregulated by lentivirus transfection, and markers of the epithelial-mesenchymal transformation (EMT) process were detected. Tumour-bearing nude mice were established with different glioma cells and treated with TMZ to measure tumour size, survival time and Ki-67 expression. Finally, the expression of IL-6 in gaMSC subpopulations and its effects on FOXS1 expression in glioma cells were also investigated. Results Conditioned media of gaMSCs promoted the proliferation, migration and chemotherapy resistance of glioma cells. The increased expression of FOXS1 and activation of the EMT process in glioma cells under gaMSC-conditioned media were detected. The relationship of FOXS1, EMT and chemotherapy resistance in glioma cells was demonstrated through the regulation of FOXS1 expression in vitro and in vivo. Moreover, FOXS1 expression in glioma cells was increased by secretion of IL-6 mainly from the CD90low gaMSC subpopulation. Conclusions CD90low gaMSCs could increase FOXS1 expression in glioma cells by IL-6 secretion, thereby activating epithelial-mesenchymal transition and resistance to TMZ in glioma cells. These results indicate a new role of gaMSCs in chemotherapy resistance and provide novel therapeutic targets.

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Long non-coding RNA FOXD2-AS1 promotes cell proliferation, metastasis and EMT in glioma by sponging miR-506-5p

Open Medicine ◽

10.1515/med-2020-0175 ◽

2020 ◽

Vol 15 (1) ◽

pp. 921-931

Author(s):

Juan Zhao ◽

Xue-Bin Zeng ◽

Hong-Yan Zhang ◽

Jie-Wei Xiang ◽

Yu-Song Liu

Keyword(s):

Cell Proliferation ◽

Epithelial Mesenchymal Transition ◽

Human Cancer ◽

Glioma Cells ◽

Suppressor Gene ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Mesenchymal Transition ◽

Non Coding Rna ◽

Long Non Coding Rna

AbstractLong non-coding RNA forkhead box D2 adjacent opposite strand RNA 1 (FOXD2-AS1) has emerged as a potential oncogene in several tumors. However, its biological function and potential regulatory mechanism in glioma have not been fully investigated to date. In the present study, RT-qPCR was conducted to detect the levels of FOXD2-AS1 and microRNA (miR)-506-5p, and western blot assays were performed to measure the expression of CDK2, cyclinE1, P21, matrix metalloproteinase (MMP)7, MMP9, N-cadherin, E-cadherin and vimentin in glioma cells. A luciferase reporter assay was performed to verify the direct targeting of miR-506-5p by FOXD2-AS1. Subsequently, cell viability was analyzed using the CCK-8 assay. Cell migration and invasion were analyzed using Transwell and wound healing assays, respectively. The results demonstrated that FOXD2-AS1 was significantly overexpressed in glioma cells, particularly in U251 cells. Knockdown of FOXD2-AS1 in glioma cells significantly inhibited cell proliferation, migration, invasion and epithelial–mesenchymal transition (EMT) and regulated the expression of CDK2, cyclinE1, P21, MMP7 and MMP9. Next, a possible mechanism for these results was explored, and it was observed that FOXD2-AS1 binds to and negatively regulates miR-506-5p, which is known to be a tumor-suppressor gene in certain human cancer types. Furthermore, overexpression of miR-506-5p significantly inhibited cell proliferation, migration, invasion and EMT, and these effects could be reversed by transfecting FOXD2-AS1 into the cells. In conclusion, our data suggested that FOXD2-AS1 contributed to glioma proliferation, metastasis and EMT via competitively binding to miR-506-5p. FOXD2-AS1 may be a promising target for therapy in patients with glioma.

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