scholarly journals Real Microgravity Influences the Cytoskeleton and Focal Adhesions in Human Breast Cancer Cells

2019 ◽  
Vol 20 (13) ◽  
pp. 3156 ◽  
Author(s):  
Mohamed Zakaria Nassef ◽  
Sascha Kopp ◽  
Markus Wehland ◽  
Daniela Melnik ◽  
Jayashree Sahana ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Live Cell Imaging ◽  
Breast Cancer Cells ◽  
Cell Imaging ◽  
Live Cell ◽  
Common Mechanism ◽  
Real Microgravity ◽  
Mcf 7 ◽  
E Cadherin

With the increasing number of spaceflights, it is crucial to understand the changes occurring in human cells exposed to real microgravity (r-µg) conditions. We tested the effect of r-µg on MCF-7 breast cancer cells with the objective to investigate cytoskeletal alterations and early changes in the gene expression of factors belonging to the cytoskeleton, extracellular matrix, focal adhesion, and cytokines. In the Technische Experimente unter Schwerelosigkeit (TEXUS) 54 rocket mission, we had the opportunity to conduct our experiment during 6 min of r-µg and focused on cytoskeletal alterations of MCF-7 breast cancer cells expressing the Lifeact-GFP marker protein for the visualization of F-actin as well as the mCherry-tubulin fusion protein using the Fluorescence Microscopy Analysis System (FLUMIAS) for fast live-cell imaging under r-µg. Moreover, in a second mission we investigated changes in RNA transcription and morphology in breast cancer cells exposed to parabolic flight (PF) maneuvers (31st Deutsches Zentrum für Luft- und Raumfahrt (DLR) PF campaign). The MCF-7 cells showed a rearrangement of the F-actin and tubulin with holes, accumulations in the tubulin network, and the appearance of filopodia- and lamellipodia-like structures in the F-actin cytoskeleton shortly after the beginning of the r-µg period. PF maneuvers induced an early up-regulation of KRT8, RDX, TIMP1, CXCL8 mRNAs, and a down-regulation of VCL after the first parabola. E-cadherin protein was significantly reduced and is involved in cell adhesion processes, and plays a significant role in tumorigenesis. Changes in the E-cadherin protein synthesis can lead to tumor progression. Pathway analyses indicate that VCL protein has an activating effect on CDH1. In conclusion, live-cell imaging visualized similar changes as those occurring in thyroid cancer cells in r-µg. This result indicates the presence of a common mechanism of gravity perception and sensation.

scholarly journals Alterations of the Cytoskeleton in Breast Cancer Cells during Microgravity visualised by FLUMIAS Live-Cell Imaging

2018 ◽  
Vol 9 ◽  
Author(s):  
Mohamed Nassef ◽  
Sascha Kopp ◽  
Daniela Melnik ◽  
Marcus Krüger ◽  
Markus Wehland ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Live Cell Imaging ◽  
Breast Cancer Cells ◽  
Cell Imaging ◽  
Live Cell

scholarly journals Synthesis and characterization of novel protein nanodots as drug delivery carriers with an enhanced biological efficacy of melatonin in breast cancer cells

RSC Advances ◽  
2021 ◽  
Vol 11 (16) ◽  
pp. 9076-9085
Author(s):  
Kanchan Yadav ◽  
Megha Das ◽  
Nurul Hassan ◽  
Archana Mishra ◽  
Jayeeta Lahiri ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Delivery ◽  
Cancer Cells ◽  
Live Cell Imaging ◽  
Biomedical Applications ◽  
Breast Cancer Cells ◽  
Cell Imaging ◽  
Synthesis And Characterization ◽  
Novel Protein

A novel nanodot-using protein has been synthesized for the live cell imaging and drug delivery of melatonin in breast cancer cells. Its unique properties hold potential for various biomedical applications in the field of bioimaging and drug delivery.

Ruthenium(II) p-cymene complex of pyridine-2-carboxaldehyde and 2-amino benzothiazole based ligand: A cytoselective and in vitro live cell imaging agent†

2021 ◽  
Author(s):  
Anuja Plavuvalapill Kumar ◽  
Priyankar Paira
Keyword(s):  
Ambient Temperature ◽  
Cancer Cells ◽  
General Formula ◽  
Live Cell Imaging ◽  
Cell Imaging ◽  
Live Cell ◽  
Imaging Agent ◽  
Arene Complexes ◽  
Mcf 7

Five Ru(II)-arene complexes ensuring the general formula [(η6-p-cymene)RuCl(k1L1-L5)(pyridine-2-carboxaldehyde)]Cl were synthesized under ambient temperature which exhibited 8-11 fold of cytoselectivity in two cancer cells (HeLa and MCF-7) with respect to normal...

scholarly journals Induced Tamoxifen Resistance is Mediated by Increased Methylation of E-Cadherin in Estrogen Receptor-Expressing Breast Cancer Cells

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Qi Wang ◽  
Melisa Gun ◽  
Xing-yu Hong
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Breast Cancers ◽  
Mesenchymal Transition ◽  
Tamoxifen Resistant ◽  
Mcf 7 ◽  
E Cadherin

Abstract Estrogen receptor-positive breast cancers are treated with tamoxifen, a drug that competitively inhibits the binding of estrogen to its receptor. Resistance to tamoxifen is a major hurdle in effective management of target breast cancer patient population. A number of dynamic changes within the tumor microenvironment, including the phenomenon of epithelial to mesenchymal transition (EMT), determine the response to endocrine therapy. EMT is marked by silencing or suppression of epithelial marker, E-Cadherin and we found significantly down-regulated E-Cadherin, among other epithelial markers, and a significantly up-regulated mesenchymal marker, Twist, among other mesenchymal markers, in a model system that comprised of tamoxifen sensitive MCF-7 cells and their tamoxifen-resistant counterparts, MCF-7-TAM, developed by chronic and escalating exposure of parental cells to tamoxifen. Further, E-cadherin, but not Twist, was differentially expressed in MCF-7-TAM cells because of differential methylation. Treatment with demethylating agent 5-azacytidine increased the expression of E-cadherin thus verifying a role of methylation in its silencing and, moreover, 5-azacytidine treatment also re-sensitized MCF-7-TAM cells to tamoxifen, as evaluated by assays for viability, apoptosis and migration potential. The 5-azacytidine effects were similar to effects of E-cadherin overexpression in MCF-7-TAM cells. This work describes novel mechanism of E-cadherin downregulation in tamoxifen resistant breast cancer cells. Further studies are needed to exploit this information for betterment of breast cancer therapy.

scholarly journals Inability of granule polarization by NK cells defines tumor resistance and can be overcome by CAR or ADCC mediated targeting

2021 ◽  
Vol 9 (1) ◽  
pp. e001334
Author(s):  
Jiri Eitler ◽  
Natalie Wotschel ◽  
Nicole Miller ◽  
Laurent Boissel ◽  
Hans G Klingemann ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Cell ◽  
Nk Cells ◽  
Cancer Cells ◽  
Live Cell Imaging ◽  
Cell Imaging ◽  
Nk Cell ◽  
Live Cell ◽  
Cell Resistance ◽  
Tumor Cell Resistance

BackgroundOn encountering a susceptible target, natural killer (NK) cells mediate cytotoxicity through highly regulated steps of directed degranulation. Cytotoxic granules converge at the microtubule organizing center and are polarized toward the immunological synapse (IS), followed by granule exocytosis. NK cell retargeting by chimeric antigen receptors (CARs) or mAbs represents a promising strategy for overcoming tumor cell resistance. However, little is known about the lytic granule dynamics of such retargeted NK cells toward NK-cell-resistant tumors.MethodsHere, we used spinning disk confocal microscopy for live-cell imaging to analyze granule-mediated NK cell cytotoxicity in ErbB2-targeted CAR-expressing NK-92 cells (NK-92/5.28.z) and high-affinity FcR transgenic NK-92 cells plus Herceptin toward ErbB2-positive breast cancer cells (MDA-MB-453), which are resistant to parental NK-92.ResultsUnmodified NK-92 cells cocultured with resistant cancer cells showed stable conjugate formation and granule clustering, but failed to polarize granules to the IS. In contrast, retargeting by CAR or FcR+Herceptin toward the MDA-MB-453 cells enabled granule polarization to the IS, resulting in highly effective cytotoxicity. We found that in NK-92 the phosphoinositide 3-kinase pathway was activated after contact with resistant MDA-MB-453, while phospholipase C-γ (PLCγ) and mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) were not activated. In contrast, retargeting by CAR or antibody-dependent cell-mediated cytotoxicity (ADCC) provided the missing PLCγ and MEK/ERK signals.ConclusionsThese observations suggest that NK cells can create conjugates with resistant cancer cells and respond by granule clustering, but the activation signals are insufficient to induce granule polarization and consequent release of lytic enzymes. Retargeting by CAR and/or the FcR/mAb (ADCC) axis provide the necessary signals, leading to granule polarization and thereby overcoming tumor cell resistance.Keywords: NK cells, NK-92, haNK, ADCC, Chimeric Antigen Receptor (CAR), breast cancer, cancer immunotherapy, live-cell imaging, granule polarization

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