scholarly journals Transdifferentiation mediated tumor suppression by the endoplasmic reticulum stress sensor IRE-1 in C. elegans

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Mor Levi-Ferber ◽  
Hai Gian ◽  
Reut Dudkevich ◽  
Sivan Henis-Korenblit
Keyword(s):  
Tumor Cell ◽  
Er Stress ◽  
Tumor Progression ◽  
Tumor Cells ◽  
Tumor Therapy ◽  
Tumor Model ◽  
Apoptosis Resistance ◽  
Stress Sensor ◽  
C Elegans ◽  
Cell Transdifferentiation

Deciphering effective ways to suppress tumor progression and to overcome acquired apoptosis resistance of tumor cells are major challenges in the tumor therapy field. We propose a new concept by which tumor progression can be suppressed by manipulating tumor cell identity. In this study, we examined the effect of ER stress on apoptosis resistant tumorous cells in a Caenorhabditis elegans germline tumor model. We discovered that ER stress suppressed the progression of the lethal germline tumor by activating the ER stress sensor IRE-1. This suppression was associated with the induction of germ cell transdifferentiation into ectopic somatic cells. Strikingly, transdifferentiation of the tumorous germ cells restored their ability to execute apoptosis and enabled their subsequent removal from the gonad. Our results indicate that tumor cell transdifferentiation has the potential to combat cancer and overcome the escape of tumor cells from the cell death machinery.

scholarly journals Activation of the NF-κB Signaling Pathway Promotes Malignancy in Bladder Cancer Cells in a Positive Feedback Manner

2020 ◽  
Author(s):  
Zhenfeng guan ◽  
Yi Sun ◽  
YaZhuo Jiang ◽  
Xinyang Wang ◽  
Jinhai Fan
Keyword(s):  
Bladder Cancer ◽  
Endothelial Cells ◽  
Tumor Cell ◽  
Tumor Progression ◽  
Signaling Pathway ◽  
Tumor Cells ◽  
Positive Feedback ◽  
Umbilical Vein

Abstract Background: The main issue arising from bladder cancer (BCa) is the high relapse ratio and tumor progression, the mechanism of which remains to be elucidated. Interaction of tumor cells with the stroma of microenvironment promoting tumor progression warrants much attention from researchers. Among all stromal cells, endothelial cells (ECs) are exceptional. Numerous studies have investigated its role of angiogenesis, but have not studied immunocyte recruitment and chemokine secretion, the important significance of which in tumor progression has been proven. Meanwhile, to the best of our knowledge, few studies have focused on the direct interaction between tumor cells and ECs in BCa tissue, which was the aim of the present study. Methods: In the present study, immunohistochemical staining is used for detecting the distribution of ECs in BCa tissue, and we use SPSS 19 to analysis the relationship between ECs distribution and tumor grade/stage; inadition, co-curlturing of tumor cell with ECs is usd to mimicking the interaction of tumor cell with ECs, followed by Chamber Assay, BrdU incorporoartion, WB, Qt-PCR, ect, to investiatin the mechanism. Results: The distribution of ECs in BCa tissue is significantly increased according to BCa grade and negatively associated to the time from BCa diagnosis to progression, manifesting as an independent risk factor for BCa prognosis. The following in vitro experiment indicates that the conditional medium from co-culture of tumor cells (T24/J82) with ECs (human umbilical vein endothelial cells, which were used as ECs in the in vitro experiment) contributes to the activation of the NF-ĸB signaling pathway in tumor cells, leading to the upregulation of CXCL1/8. This further results in enhanced tumor cell malignancy and EC recruitment, manifested as a positive feedback loop. Conclusions: The present study provided a further understanding on the role of ECs in BCa progression—not only by angiogenesis but also by interacting with tumor cell dirctly.

scholarly journals Neuronal regulated Ire1-dependent mRNA decay controls germline differentiation in C. elegans

2020 ◽  
Author(s):  
Mor Levi-Ferber ◽  
Rewayd Shalash ◽  
Adrien Le-Thomas ◽  
Yehuda Salzberg ◽  
Maor Shurgi ◽  
...  
Keyword(s):  
Er Stress ◽  
Tumor Cells ◽  
Cell Fate ◽  
Germ Cells ◽  
Mrna Decay ◽  
Neuronal Circuit ◽  
C Elegans ◽  
Animal Physiology ◽  
Molecular Events ◽  
Germline Differentiation

Understanding the molecular events that regulate cell pluripotency versus acquisition of differentiated somatic cell fate is fundamentally important. Studies in C. elegans demonstrate that knockout of the germline-specific translation repressor gld-1, causes germ cells within tumorous gonads to form germline-derived teratoma. Previously we demonstrated that ER stress enhances this phenotype to suppress germline tumor progression (Levi-Ferber M, 2015). Here, we identify a neuronal circuit that non-autonomously suppresses germline differentiation, and show that it communicates with the gonad via the neurotransmitter serotonin to limit somatic differentiation of the tumorous germline. ER stress controls this circuit through regulated IRE-1-dependent mRNA decay of transcripts encoding the neuropeptide FLP-6. Depletion of FLP-6 disrupts the circuit's integrity and hence its ability to prevent somatic-fate acquisition by germline tumor cells. Our findings reveal mechanistically how ER stress enhances ectopic germline differentiation, and demonstrate that RIDD can affect animal physiology by controlling a specific neuronal circuit.

scholarly journals CYTOTOXIC PROPERTIES OF NANOSTRUCTURES BASED ON ALUMINUM OXIDE AND HYDROXIDE PHASES IN RELATION TO TUMOR CELLS

2021 ◽  
Vol 20 (4) ◽  
pp. 73-83
Author(s):  
A. S. Lozhkomoev ◽  
O. V. Bakina ◽  
S. O. Kazantsev ◽  
L. Yu. Ivanova ◽  
A. V. Avgustinovich ◽  
...  
Keyword(s):  
Phase Composition ◽  
Antitumor Activity ◽  
Tumor Cell ◽  
Cell Viability ◽  
Tumor Cells ◽  
Tumor Therapy ◽  
Nitrogen Atmosphere ◽  
Acid Base ◽  
Cell Microenvironment ◽  
Base Properties

Background. Currently, the use of nanoparticles and nanostructures as components of tumor therapy is the subject of numerous scientific articles. To change the parameters of cell microenvironment in presence of nanoparticles and nanostructures is a promising approach to reducing the tumor cell viability. Aluminum hydroxides and oxides have a number of advantages over other particles due to their porous surface, low toxicity, and thermal stability.The purpose of the study was to investigate the influence of the acid-base properties of aluminum hydroxide structures with different phase composition on the tumor cell viability (Hela, mda, pymt, a549, B16F10).Material and methods. Aln/al nanoparticles were used as a precursor for obtaining structures with various phase compositions. The anoparticles were produced by electric explosion of an aluminum wire in a nitrogen atmosphere. Such nanoparticles interact with water at 60 °Ϲ, resulting in formation of porous nanostructures. They are agglomerates of nanosheets with a planar size of up to 200 nm and a thickness of 5 nm. The phase composition of the structures was varied by the calcination temperature. A change in the phase composition of nanostructures led to a change in the acid-base properties of their surface. To estimate the number of acidic and basic centers on the surface of nanostructures, the adsorption of Hammett indicators was used. The amount of adsorbed dyes was determined spectrophotometrically.Results. It was found that the differences in the acid-base characteristics of the surface of the nanostructures led to a change in their antitumor activity. Γ-al2o3 had 6.5 times more basic centers than acidic ones, which determined its ability to exhibit more pronounced antacid properties, i.e. Longer to neutralize protons secreted by tumor cells. This sample had the highest antitumor activity against all tested cell lines.Conclusion. The antitumor activity of synthesized structures was found to be related not only to an increase in the ph of the cell microenvironment, but also to the ability to maintain the alkalinity of the microenvironment for a longer time due to the adsorption of protons released by tumor cells.

Sapphyrins Exhibit Tumor Selectivity and Efficacy in Animal Models of Hematologic Malignancies.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2501-2501
Author(s):  
Louie Naumovski ◽  
Mint Sirisawad ◽  
Philip Lecane ◽  
Jason Ramos ◽  
Darren Magda ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Complete Blood Count ◽  
Parent Compound ◽  
Tumor Model ◽  
Hematologic Malignancies ◽  
Drug Uptake ◽  
Tumor Control ◽  
Relative Uptake

Abstract Sapphyrins are pentapyrrolic metal-free expanded porphyrins that localize to tumors. We have previously demonstrated that sapphyrins induce apoptosis in a variety of hematologic tumor cell lines including lymphomas (Ramos, DHL-4, HF-1), leukemias (Jurkat, HL-60), and myelomas (8226/S, 1-310, C2E3, 1-414). Through chemical modification of the parent compound, PCI-2000, a number of derivatives were generated and tested for induction of apoptosis in Ramos cells. PCI-2000 and one of the more potent apoptosis-inducing derivatives, PCI-2050, were injected into CD-1 nude mice bearing Ramos xenografts. Animals were sacrificed 48 hrs after injection and analyzed for drug uptake in the tumor, liver and spleen using flow cytometry. For PCI-2000, the relative uptake was spleen>tumor>liver. For PCI-2050 the relative uptake was tumor>spleen>liver, suggesting that PCI-2050 preferentially localizes in tumors compared to PCI-2000. Tumor cells isolated from PCI-2050 treated animals grew less well in culture and had more apoptotic cells than those derived from PCI-2000 or control animals. Uptake of PCI-2050 into xenograft tumor cells and tumor cell killing was dose dependent. PCI-2050 (10 umol/kg x 2 days in a row) was administered to Ramos xenograft bearing animals that were then monitored for tumor growth. In both minimal tumor (animals treated before tumor was palpable) and established tumor (palpable tumor) models, PCI-2050 reduced tumor growth by 60–75%. Alternative dosing strategies revealed that split dosing (allowing 1 or more days between doses) was more efficacious in tumor control than dosing 2 days in a row. At the doses used in this study, there was no myelosuppression or lymphosuppression, hepatic or renal abnormalities as assessed by complete blood count and comprehensive serum chemistry analysis, respectively. Our work demonstrates that PCI-2050 induces apoptosis in tissue culture and inhibits tumor growth in an animal tumor model while exhibiting minimal toxicity. PCI-2050 and other sapphyrin derivatives will be further evaluated as potential anti-cancer agents.

scholarly journals Development of Tumor Cell-Based Vaccine with IL-12 Gene Electrotransfer as Adjuvant

Vaccines ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 111
Author(s):  
Tinkara Remic ◽  
Gregor Sersa ◽  
Katja Ursic ◽  
Maja Cemazar ◽  
Urska Kamensek
Keyword(s):  
Tumor Cell ◽  
Tumor Cells ◽  
Tumor Vaccine ◽  
Tumor Model ◽  
Interleukin 12 ◽  
Gene Electrotransfer ◽  
Tumor Models ◽  
Tumor Irradiation ◽  
Tumor Outgrowth ◽  
Ct26 Tumor

Tumor cell-based vaccines use tumor cells as a source of tumor-associated antigens. In our study, we aimed to develop and test a tumor vaccine composed of tumor cells killed by irradiation combined with in vivo interleukin-12 gene electrotransfer as an adjuvant. Vaccination was performed in the skin of B16-F10 malignant melanoma or CT26 colorectal carcinoma tumor-bearing mice, distant from the tumor site and combined with concurrent tumor irradiation. Vaccination was also performed before tumor inoculation in both tumor models and tumor outgrowth was followed. The antitumor efficacy of vaccination in combination with tumor irradiation or preventative vaccination varied between the tumor models. A synergistic effect between vaccination and irradiation was observed in the B16-F10, but not in the CT26 tumor model. In contrast, up to 56% of mice were protected from tumor outgrowth in the CT26 tumor model and none were protected in the B16-F10 tumor model. The results suggest a greater contribution of the therapeutic vaccination to tumor irradiation in a less immunogenic B16-F10 tumor model, in contrast to preventative vaccination, which has shown greater efficacy in a more immunogenic CT26 tumor model. Upon further optimization of the vaccination and irradiation regimen, our vaccine could present an alternative tumor cell-based vaccine.

scholarly journals Production of a Monoclonal Antibody Directed against the Recombinant SEL1L Protein

2002 ◽  
Vol 17 (2) ◽  
pp. 104-111 ◽  
Author(s):  
R. Orlandi ◽  
M. Cattaneo ◽  
F. Troglio ◽  
M. Campiglio ◽  
I. Biunno ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Tumor Growth ◽  
Tumor Progression ◽  
Tumor Cells ◽  
Western Blotting ◽  
Human Gene ◽  
Recombinant Fragment ◽  
C Elegans ◽  
Normal Tissues ◽  
N Terminus

SEL1L, highly similar to the C. elegans sel-1 gene, is a recently cloned human gene whose function is under investigation. SEL1L is differentially expressed in tumors and normal tissues and seems to play a role in tumor growth and aggressiveness. We used the recombinant N-terminus of the SEL1L protein to immunize a Balb/c mouse and produce a monoclonal antibody. A hybridoma secreting an antibody specifically reacting on the SEL1L recombinant fragment was selected. This monoclonal antibody, named MSel1, recognizes the SEL1L protein by Western blotting, immunofluorescence and immunohistochemistry on normal and tumor cells. MSel1 is able to recognize SEL1L even on archival tumor specimens and is therefore particularly appropriate to study SEL1L involvement in tumor progression.

scholarly journals Homologous tumor cell membrane vesicles active preferential self-recognition of tumor cells in vitro

2022 ◽  
Vol 65 (1) ◽  
Author(s):  
Chenghu Wu ◽  
Ailin Yu ◽  
Yue Chen ◽  
Mingbo Fan
Keyword(s):  
Cell Membrane ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Tumor Therapy ◽  
Membrane Vesicles ◽  
Membrane System ◽  
Tumor Cell Membrane ◽  
Self Recognition

AbstractCell membrane vesicles, as delivery carriers of drugs or biological agents in vivo, are an important therapeutic mode in the study of disease treatment. Tumor membrane-derived vesicles have been widely used in tumor therapy because of their good tumor enrichment effect. The most common method is the surface of nanoparticles coated with tumor cell membrane, which can effectively prolong the circulation time of particles in the blood and the enrichment of tumors. In this study, we prepared vesicles of different tumor cell membrane derivate and studied their targeting to tumors detailly. The results showed that homologous vesicles have high targeting to homologous tumor cells. The fluorescence of vesicles in homologous tumor cells was significantly higher than that in other tumor cells. This study will provide a new strategy and guidance for the clinical treatment of cancer based on the tumor cell membrane system. Graphical Abstract

Interaction of Human Tumor Cells with Human Platelets and the Coagulation System

1983 ◽  
Vol 50 (03) ◽  
pp. 726-730 ◽  
Author(s):  
Hamid Al-Mondhiry ◽  
Virginia McGarvey ◽  
Kim Leitzel
Keyword(s):  
Tumor Cell ◽  
Tumor Cells ◽  
Cell Lines ◽  
Human Tumor ◽  
Human Platelets ◽  
Factor Vii ◽  
Coagulation System ◽  
Breast Adenocarcinoma ◽  
Activate Factor ◽  
Tumor Cell Lines

SummaryThis paper reports studies on the interaction between human platelets, the plasma coagulation system, and two human tumor cell lines grown in tissue culture: Melanoma and breast adenocarcinoma. The interaction was monitored through the use of 125I- labelled fibrinogen, which measures both thrombin activity generated by cell-plasma interaction and fibrin/fibrinogen binding to platelets and tumor cells. Each tumor cell line activates both the platelets and the coagulation system simultaneously resulting in the generation of thrombin or thrombin-like activity. The melanoma cells activate the coagulation system through “the extrinsic pathway” with a tissue factor-like effect on factor VII, but the breast tumor seems to activate factor X directly. Both tumor cell lines activate platelets to “make available” a platelet- derived procoagulant material necessary for the conversion of prothrombin to thrombin. The tumor-derived procoagulant activity and the platelet aggregating potential of cells do not seem to be inter-related, and they are not specific to malignant cells.

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