scholarly journals Role of tumor cell senescence in non-professional phagocytosis and cell-in-cell structure formation

2020 ◽  
Author(s):  
Dorian Gottwald ◽  
Florian Putz ◽  
Nora Hohmann ◽  
Maike Büttner-Herold ◽  
Markus Hecht ◽  
...  
Keyword(s):  
Rectal Carcinoma ◽  
Cell Structure ◽  
Tumor Therapy ◽  
Carcinoma Cells ◽  
Pancreas Carcinoma ◽  
Poor Prognostic Factor ◽  
Long Time

Abstract Background: Non-professional phagocytosis is usually triggered by stimuli such as necrotic cell death. In tumor therapy, the tumors often disappear slowly and only long time after the end of therapy. Here, tumor therapy inactivates the cells by inducing senescence. Therefore, study focused whether senescence is a stimulus for non-professional phagocytosis or whether senescent cells themselves phagocytize non-professionally.Results: Senescence was induced in cell lines by camptothecin and a phagocytosis assay was performed. In tissue of a cohort of 192 rectal cancer patients senescence and non-professional phagocytosis was studied by anti-histone H3K9me3 and anti-E-cadherin staining. Senescent fibroblasts and pancreas carcinoma cells phagocytize necrotic cells but are not phagocytized. In the tissue of rectal carcinoma, senescent cells can phagocytize and can be phagocytized. A high number of senescent cells and, at the same time, high numbers of non-professional phagocytizing cells in the rectal carcinoma tissue lead to an extremely unfavorable prognosis regarding overall survival.Conclusion: Senescent cells can be non-professionally phagocytized and at the same time they can non-professionally phagocytize in vivo. In vitro experiments indicate that it is unlikely that senescence is a strong trigger for non-professional phagocytosis. Combined high rates of non-professional phagocytosis and high rates of senescence are an extremely poor prognostic factor for overall survival.

scholarly journals Role of tumor cell senescence in non-professional phagocytosis and cell-in-cell structure formation

2020 ◽  
Author(s):  
Dorian Gottwald ◽  
Florian Putz ◽  
Nora Hohmann ◽  
Maike Büttner-Herold ◽  
Markus Hecht ◽  
...  
Keyword(s):  
Rectal Carcinoma ◽  
Cell Structure ◽  
Tumor Therapy ◽  
Carcinoma Cells ◽  
Pancreas Carcinoma ◽  
Poor Prognostic Factor ◽  
Long Time

Abstract Background: Non-professional phagocytosis is usually triggered by stimuli such as necrotic cell death. In tumor therapy, the tumors often disappear slowly and only long time after the end of therapy. Here, tumor therapy inactivates the cells by inducing senescence. Therefore, study focused whether senescence is a stimulus for non-professional phagocytosis or whether senescent cells themselves phagocytize non-professionally.Results: Senescence was induced in cell lines by camptothecin and a phagocytosis assay was performed. In tissue of a cohort of 192 rectal cancer patients senescence and non-professional phagocytosis was studied by anti-histone H3K9me3 and anti-E-cadherin staining. Senescent fibroblasts and pancreas carcinoma cells phagocytize necrotic cells but are not phagocytized. In the tissue of rectal carcinoma, senescent cells can phagocytize and can be phagocytized. A high number of senescent cells and, at the same time, high numbers of non-professional phagocytizing cells in the rectal carcinoma tissue lead to an extremely unfavorable prognosis regarding overall survival.Conclusion: Senescent cells can be non-professionally phagocytized and at the same time they can non-professionally phagocytize in vivo. In vitro experiments indicate that it is unlikely that senescence is a strong trigger for non-professional phagocytosis. Combined high rates of non-professional phagocytosis and high rates of senescence are an extremely poor prognostic factor for overall survival.

scholarly journals Role of tumor cell senescence in non-professional phagocytosis and cell-in-cell structure formation

2020 ◽  
Author(s):  
Dorian Gottwald ◽  
Florian Putz ◽  
Nora Hohmann ◽  
Maike Büttner-Herold ◽  
Markus Hecht ◽  
...  
Keyword(s):  
Overall Survival ◽  
Rectal Carcinoma ◽  
Cell Structure ◽  
Tumor Therapy ◽  
Pancreas Carcinoma ◽  
Poor Prognostic Factor ◽  
Long Time

Abstract Background: Non-professional phagocytosis is usually triggered by stimuli such as necrotic cell death. In tumor therapy, the tumors often disappear slowly and only long time after the end of therapy. Here, tumor therapy inactivates the cells by inducing senescence. Therefore, study focused whether senescence is a stimulus for non-professional phagocytosis or whether senescent cells themselves phagocytize non-professionally. Results: Senescence was induced in cell lines by camptothecin and a phagocytosis assay was performed. In tissue of a cohort of 192 rectal cancer patients senescence and non-professional phagocytosis was studied by anti-histone H3K9me3 and anti-E-cadherin staining. Senescent fibroblasts and pancreas carcinoma cells phagocytize necrotic cells but are not phagocytized. In the tissue of rectal carcinoma, senescent cells can phagocytize and can be phagocytized. A high number of senescent cells and, at the same time, high numbers of non-professional phagocytizing cells in the rectal carcinoma tissue lead to an extremely unfavorable prognosis regarding overall survival. Conclusion: Senescent cells can be non-professionally phagocytized and at the same time they can non-professionally phagocytize in vivo. In vitro experiments indicate that it is unlikely that senescence is a strong trigger for non-professional phagocytosis. Combined high rates of non-professional phagocytosis and high rates of senescence are an extremely poor prognostic factor for overall survival.

scholarly journals Role of tumor cell senescence in non-professional phagocytosis and cell-in-cell structure formation

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Dorian Gottwald ◽  
Florian Putz ◽  
Nora Hohmann ◽  
Maike Büttner-Herold ◽  
Markus Hecht ◽  
...  
Keyword(s):  
Overall Survival ◽  
Rectal Carcinoma ◽  
Cell Structure ◽  
Tumor Therapy ◽  
Pancreas Carcinoma ◽  
Poor Prognostic Factor ◽  
Long Time

Abstract Background Non-professional phagocytosis is usually triggered by stimuli such as necrotic cell death. In tumor therapy, the tumors often disappear slowly and only long time after the end of therapy. Here, tumor therapy inactivates the cells by inducing senescence. Therefore, study focused whether senescence is a stimulus for non-professional phagocytosis or whether senescent cells themselves phagocytize non-professionally. Results Senescence was induced in cell lines by camptothecin and a phagocytosis assay was performed. In tissue of a cohort of 192 rectal cancer patients senescence and non-professional phagocytosis was studied by anti-histone H3K9me3 and anti-E-cadherin staining. Senescent fibroblasts and pancreas carcinoma cells phagocytize necrotic cells but are not phagocytized. In the tissue of rectal carcinoma, senescent cells can phagocytize and can be phagocytized. A high number of senescent cells and, at the same time, high numbers of non-professional phagocytizing cells in the rectal carcinoma tissue lead to an extremely unfavorable prognosis regarding overall survival. Conclusion Senescent cells can be non-professionally phagocytized and at the same time they can non-professionally phagocytize in vivo. In vitro experiments indicate that it is unlikely that senescence is a strong trigger for non-professional phagocytosis. Combined high rates of non-professional phagocytosis and high rates of senescence are an extremely poor prognostic factor for overall survival.

scholarly journals Role of tumor cell senescence in non-professional phagocytosis and cell-in-cell structure formation

2020 ◽  
Author(s):  
Dorian Gottwald ◽  
Florian Putz ◽  
Nora Hohmann ◽  
Maike Büttner-Herold ◽  
Markus Hecht ◽  
...  
Keyword(s):  
Overall Survival ◽  
Rectal Carcinoma ◽  
Cell Structure ◽  
Tumor Therapy ◽  
Pancreas Carcinoma ◽  
Poor Prognostic Factor ◽  
Long Time

Abstract Non-professional phagocytosis is usually triggered by stimuli such as necrotic cell death. In tumor therapy, the tumors often disappear slowly and only long time after the end of therapy. Here, tumor therapy inactivates the cells by inducing senescence. Therefore, study focused whether senescence is a stimulus for non-professional phagocytosis or whether senescent cells themselves phagocytize non-professionally. Senescence was induced in cell lines by camptothecin and a phagocytosis assay was performed. In tissue of a cohort of 192 rectal cancer patients senescence and non-professional phagocytosis was studied by anti-histone H3K9me3 and anti-E-cadherin staining. Senescent fibroblasts and pancreas carcinoma cells phagocytize necrotic cells but are not phagocytized. In the tissue of rectal carcinoma, senescent cells can phagocytize and can be phagocytized. A high number of senescent cells and, at the same time, high numbers of non-professional phagocytizing cells in the rectal carcinoma tissue lead to an extremely unfavorable prognosis regarding overall survival. Senescent cells can be non-professionally phagocytized and at the same time they can non-professionally phagocytize in vivo. In vitro experiments indicate that it is unlikely that senescence is a strong trigger for non-professional phagocytosis. Combined high rates of non-professional phagocytosis and high rates of senescence are an extremely poor prognostic factor for overall survival.

scholarly journals Metformin sensitizes the response of oral squamous cell carcinoma to cisplatin treatment through inhibition of NF-κB/HIF-1α signal axis

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Xiaofeng Qi ◽  
Wengguang Xu ◽  
Junqi Xie ◽  
Yufeng Wang ◽  
Shengwei Han ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Carcinoma Cells ◽  
Oral Cancers ◽  
Underlying Mechanisms

Abstract Resistance towards chemotherapy is a common complication in treatment of oral cancers, which leads to treatment failure and poor outcome. In recent years, a growing body of evidence has shown that tumour hypoxia significantly contributes to chemoresistance. Metformin, a widely used oral hypoglycaemic drug, can reportedly potentiate the efficacy of chemotherapeutic drugs in various cancers; however, the underlying mechanisms are intricate and have not been fully understood. In this study, we explored the role of metformin in chemosensitivity of oral squamous cell carcinoma cells (OSCC) to cisplatin both in vitro and in vivo, and attempted to elucidate its possible underlying mechanisms. Encouragingly, we found that metformin synergistically enhanced cisplatin cytotoxicity and reversed the chemoresistance to certain extent. This mechanism could likely be related with inhibition of the NF-κB/HIF-1α signal axis and lead to the downregulation of hypoxia-regulated genes products. Therefore, metformin could serve as a chemosensitiser for cisplatin-based regimens for OSCC, thereby providing a theoretical basis for future use in the treatment of oral cancers.

Transcription factor STAT1 promotes the proliferation, migration and invasion of nasopharyngeal carcinoma cells by upregulating LINC01160

2020 ◽  
Author(s):  
Jingang Ai ◽  
Guolin Tan ◽  
Tiansheng Wang ◽  
Wei Li ◽  
Ru Gao ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Nasopharyngeal Carcinoma ◽  
Chromatin Immunoprecipitation ◽  
Malignant Cell ◽  
Carcinoma Cells ◽  
Migration And Invasion ◽  
Cell Phenotype

Aim: To investigate the role of LINC01160 in nasopharyngeal carcinoma (NPC). Materials & methods: Using NPC cells CNE-2 and HNE-2 in vitro, we performed quantitative PCR to determine mRNA expression and western blotting to determine protein expression. CCK-8, transwell, flow cytometry and wound healing assays were done to examine the function of LINC01160 and STAT1. Chromatin immunoprecipitation PCR (ChIP-PCR) confirmed that STAT1 combines with the LINC01160 promoter region. Xenograft experiments were used to verify the role of STAT1 and LINC01160 in vivo. Results: LINC01160 is upregulated in NPC and can promote a malignant cell phenotype. STAT1 is a transcription factor of LINC01160 and can promote a malignant cell phenotype through upregulating LINC01160 expression. Conclusion: STAT1 can promote a malignant cell phenotype by upregulating LINC01160.

scholarly journals Role of the Exosome Secretion Machinery in Ovarian Carcinoma: In Vitro and In Vivo Models

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Esther Channah Broner ◽  
Hadil Onallah ◽  
Tali Tavor Re’em ◽  
Ben Davidson ◽  
Reuven Reich
Keyword(s):  
Ovarian Carcinoma ◽  
Mrna Expression ◽  
Carcinoma Cells ◽  
Serous Carcinoma ◽  
Clinical Role ◽  
In Vivo Models ◽  
Ovarian Carcinoma Cells

Objective. We recently reported on the expression and clinical role of molecules that mediate exosome secretion in high-grade serous carcinoma. In the present study, the biological role of these molecules was analyzed. Methods. OVCAR8 and ES-2 ovarian carcinoma cells were studied using a combination of CRISPR/Cas9 technology and two 3D in vitro models—spheroids emulating effusions and alginate scaffolds representing solid lesions. Isolation of exosomes was validated by electron microscopy. TSAP6, NSMASE2, RAB27A, and RAB27B mRNA and protein levels were analyzed using qRT-PCR and Western blotting, respectively. Tumor aggressiveness was studied in vitro using scratch assay, invasion assay, and matrix metalloproteinase (MMP) activity assay and in vivo using a mouse model. Results. In OVCAR8 cells, mRNA expression of TSAP6 and RAB27A was significantly higher in spheroids compared to scaffolds, whereas the opposite was true for NSMASE2 mRNA. In ES-2 cells, TSAP6 and RAB27B mRNA expression was significantly higher in spheroids versus scaffolds. In addition, nSMase2 and TSAP6 protein expression was significantly higher in scaffolds compared to spheroids. CRISPR-edited cells with silencing of NSMASE2, TSAP6, and RAB27A/B had reduced migration, invasion, and MMP activity. Additionally, knockout (KO) of these molecules resulted in significantly diminished exosome secretion. In vivo assay showed that when injected to mice, OVCAR8 RAB27A/B KO cells, as opposed to control OVCAR8 cells, did not form ascites or visible tumor lesions and had reduced MMP expression. Conclusion. The present study provides evidence that different models for culturing ovarian carcinoma cells affect the expression of molecules mediating exosome secretion and that these molecules have a tumor-promoting role. Silencing these molecules may consequently have therapeutic relevance in this cancer.

scholarly journals BNIP3L-Dependent Mitophagy Promotes HBx-Induced Cancer Stemness of Hepatocellular Carcinoma Cells via Glycolysis Metabolism Reprogramming

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 655 ◽  
Author(s):  
Yuan-Yuan Chen ◽  
Wei-Hua Wang ◽  
Lin Che ◽  
You Lan ◽  
Li-Yin Zhang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Energy Homeostasis ◽  
Side Population ◽  
Carcinoma Cells ◽  
Cancer Stemness ◽  
B Virus ◽  
Hcc Cells

Hepatitis B virus (HBV) is one of predisposing factors for hepatocellular carcinoma (HCC). The role of HBV x protein (HBx) in mediating the induction and maintenance of cancer stemness during HBV-related HCC attracts considerable attention, but the exact mechanism has not been clearly elucidated. Here, ABCG2-dependent stem-like side population (SP) cells, which are thought to be liver cancer stem cells (LCSCs), were present in HCC cells, and the fraction of this subset was increased in HBx-expressing HCC cells. In addition, glycolysis was upregulated in LCSCs and HBx-expressing HCC cells, and intervention of glycolysis attenuated cancer stem-like phenotypes. Mitochondria play an important role in the maintenance of energy homeostasis, BNIP3L-dependent mitophagy was also activated in LCSCs and HBx-expressing HCC cells, which triggered a metabolic shift toward glycolysis. In summary, we proposed a positive feedback loop, in which HBx induced BNIP3L-dependent mitophagy which upregulated glycolytic metabolism, increasing cancer stemness of HCC cells in vivo and in vitro. BNIP3L might be a potential therapeutic target for intervention of LCSCs-associated HCC. Anti-HBx, a monoclonal antibody targeting intracellular HBx, had the potential to delay the progression of HBV infection related-HCC.

scholarly journals MT1JP-mediated miR-24-3p/BCL2L2 axis promotes Lenvatinib resistance in hepatocellular carcinoma cells by inhibiting apoptosis

2021 ◽  
Author(s):  
Ting Yu ◽  
Jiajian Yu ◽  
Lu Lu ◽  
Yize Zhang ◽  
Yadong Zhou ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Feedback Loop ◽  
Carcinoma Cells ◽  
Advanced Hepatocellular Carcinoma ◽  
Apoptotic Protein ◽  
Non Coding Rnas ◽  
Hcc Cells

Abstract Purpose Lenvatinib is a long-awaited alternative to Sorafenib for first-line targeted therapy of patients with advanced hepatocellular carcinoma (HCC). However, resistance to Lenvatinib results in tumor progression and has become a major obstacle to improving the prognosis of HCC patients. Exploring the mechanisms underlying Lenvatinib resistance is considered essential for the treatment of advanced HCC. Methods Lenvatinib resistant HCC (LR-HCC) cells were generated and potential long non-coding RNAs (Lnc-RNAs) upregulated in LR-HCC cells were identified by RNA sequencing. The effects of upregulated Lnc-RNAs were evaluated in vitro in cell models and in vivo in experimental animals using quantitative cell viability and apoptosis assays. Results We found that Lnc-RNA MT1JP (MT1JP) was upregulated in LR-HCC cells and inhibited the apoptosis signaling pathway. In addition, we found that sponging of microRNA-24-3p by MT1JP released Bcl-2 like 2 (BCL2L2), an anti-apoptotic protein, thereby forming a positive-feedback loop. The role of this feedback loop was validated using rescue assays. Additionally, we found that upregulation of MT1JP and BCL2L2 impaired the sensitivity of HCC cells to Lenvatinib both vitro and vivo. Conclusions Our results suggest a novel molecular feedback loop between MT1JP and apoptosis signaling in Lenvatinib sensitive HCC cells.

Ganoderma lucidum Polysaccharides: Immunomodulation and Potential Anti-Tumor Activities

2011 ◽  
Vol 39 (01) ◽  
pp. 15-27 ◽  
Author(s):  
Zengtao Xu ◽  
Xiuping Chen ◽  
Zhangfeng Zhong ◽  
Lidian Chen ◽  
Yitao Wang
Keyword(s):  
Ganoderma Lucidum ◽  
Tumor Therapy ◽  
White Rot ◽  
In Vivo Studies ◽  
White Rot Fungus ◽  
Bioactive Substances ◽  
Cytotoxic Effects

Ganoderma lucidum (G. lucidum), a basidiomycete white rot fungus, has long been prescribed to prevent and treat various human diseases, particularly in China, Japan, and Korea. Several classes of bioactive substances have been isolated and identified from G. lucidum, such as triterpenoids, polysaccharides, nucleosides, sterols, and alkaloids, among others. This paper examines the potential role of G. lucidum polysaccharide (GLPS) in tumor therapy and the possible mechanisms involved. Both in vitro and in vivo studies suggested that the anti-tumor activities of GLPS are mediated by its immunomodulatory, anti-angiogenic, and cytotoxic effects. GLPS affects immune cells and immune-related cells including B lymphocytes, T lymphocytes, dendritic cells, macrophages, and natural killer cells. In addition, recent data also suggest that GLPS suppresses tumorigenesis or inhibits tumor growth through direct cytotoxic effect and anti-angiogenic actions. However, many questions still need to be answered before both G. lucidum and GLPS can be widely accepted and used as anti-tumor agents.

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