scholarly journals Feet on the Ground: Physical Support of the Inner Retina Is a Strong Determinant for Cell Survival and Structural Preservation In Vitro

2014 ◽  
Vol 55 (4) ◽  
pp. 2200 ◽  
Author(s):  
Linnéa Taylor ◽  
Karin Arnér ◽  
Ingrid Holmgren Taylor ◽  
Fredrik Ghosh
Keyword(s):  
Cell Survival ◽  
Inner Retina ◽  
Physical Support ◽  
Structural Preservation

The warburg effect and tumour cell survival in human GBMs

2007 ◽  
Vol 30 (4) ◽  
pp. 97 ◽  
Author(s):  
A Wolf ◽  
J Mukherjee ◽  
A Guha
Keyword(s):  
Cytochrome C ◽  
Cell Survival ◽  
Expression Profile ◽  
Tumour Cell ◽  
Warburg Effect ◽  
Glycolytic Enzymes ◽  
Cytochrome C Release ◽  
Apoptotic Pathway ◽  
The Warburg Effect

Introduction: GBMs are resistant to apoptosis induced by the hypoxic microenvironment and standard therapies including radiation and chemotherapy. We postulate that the Warburg effect, a preferential glycolytic phenotype of tumor cells even under aerobic conditions, plays a role in these aberrant pro-survival signals. In this study we quantitatively examined the expression profile of hypoxia-related glycolytic genes within pathologically- and MRI-defined “centre” and “periphery” of GBMs. We hypothesize that expression of hypoxia-induced glycolytic genes, particularly hexokinase 2 (HK2), favours cell survival and modulates resistance to tumour cell apoptosis by inhibiting the intrinsic mitochondrial apoptotic pathway. Methods: GBM patients underwent conventional T1-weighted contrast-enhanced MRI and MR spectroscopy studies on a 3.0T GE scanner, prior to stereotactic sampling (formalin and frozen) from regions which were T1-Gad enhancing (“centre”) and T2-positive, T1-Gad negative (“periphery”). Real-time qRT-PCR was performed to quantify regional gene expression of glycolytic genes including HK2. In vitro functional studies were performed in U87 and U373 GBM cell lines grown in normoxic (21% pO2) and hypoxic (< 1%pO2) conditions, transfected with HK2 siRNA followed by measurement of cell proliferation (BrdU), apoptosis (activated caspase 3/7, TUNEL, cytochrome c release) and viability (MTS assay). Results: There exists a differential expression profile of glycolytic enzymes between the hypoxic center and relatively normoxic periphery of GBMs. Under hypoxic conditions, there is increased expression of HK2 at the mitochondrial membrane in GBM cells. In vitro HK2 knockdown led to decreased cell survival and increased apoptosis via the intrinsic mitochondrial pathway, as seen by increased mitochondrial release of cytochrome-C. Conclusions: Increased expression of HK2 in the centre of GBMs promotes cell survival and confers resistance to apoptosis, as confirmed by in vitro studies. In vivo intracranial xenograft studies with injection of HK2-shRNA are currently being performed. HK2 and possibly other glycolytic enzymes may provide a target for enhanced therapeutic responsiveness thereby improving prognosis of patients with GBMs.

scholarly journals Macropinocytosis requires Gal-3 in a subset of patient-derived glioblastoma stem cells

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Laetitia Seguin ◽  
Soline Odouard ◽  
Francesca Corlazzoli ◽  
Sarah Al Haddad ◽  
Laurine Moindrot ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Survival ◽  
Small Gtpases ◽  
Molecular Signature ◽  
Carbohydrate Binding ◽  
Pancreatic Cancers ◽  
Galectin 3 ◽  
Pharmacologic Inhibition

AbstractRecently, we involved the carbohydrate-binding protein Galectin-3 (Gal-3) as a druggable target for KRAS-mutant-addicted lung and pancreatic cancers. Here, using glioblastoma patient-derived stem cells (GSCs), we identify and characterize a subset of Gal-3high glioblastoma (GBM) tumors mainly within the mesenchymal subtype that are addicted to Gal-3-mediated macropinocytosis. Using both genetic and pharmacologic inhibition of Gal-3, we showed a significant decrease of GSC macropinocytosis activity, cell survival and invasion, in vitro and in vivo. Mechanistically, we demonstrate that Gal-3 binds to RAB10, a member of the RAS superfamily of small GTPases, and β1 integrin, which are both required for macropinocytosis activity and cell survival. Finally, by defining a Gal-3/macropinocytosis molecular signature, we could predict sensitivity to this dependency pathway and provide proof-of-principle for innovative therapeutic strategies to exploit this Achilles’ heel for a significant and unique subset of GBM patients.

scholarly journals Cell-derived Extracellular Matrix as maintaining Biomaterial for adipogenic differentiation

2020 ◽  
Vol 6 (3) ◽  
pp. 410-413
Author(s):  
Petra J. Kluger ◽  
Svenja Nellinger ◽  
Simon Heine ◽  
Ann-Cathrin Volz
Keyword(s):  
Tissue Engineering ◽  
Extracellular Matrix ◽  
Adipogenic Differentiation ◽  
Cellular Activity ◽  
Adipose Tissue Engineering ◽  
Physical Support ◽  
Supporting Effect ◽  
Brdu Assay ◽  
The Impact

AbstractThe extracellular matrix (ECM) naturally surrounds cells in humans, and therefore represents the ideal biomaterial for tissue engineering. ECM from different tissues exhibit different composition and physical characteristics. Thus, ECM provides not only physical support but also contains crucial biochemical signals that influence cell adhesion, morphology, proliferation and differentiation. Next to native ECM from mature tissue, ECM can also be obtained from the in vitro culture of cells. In this study, we aimed to highlight the supporting effect of cell-derived- ECM (cdECM) on adipogenic differentiation. ASCs were seeded on top of cdECM from ASCs (scdECM) or pre-adipocytes (acdECM). The impact of ECM on cellular activity was determined by LDH assay, WST I assay and BrdU assay. A supporting effect of cdECM substrates on adipogenic differentiation was determined by oil red O staining and subsequent quantification. Results revealed no effect of cdECM substrates on cellular activity. Regarding adipogenic differentiation a supporting effect of cdECM substrates was obtained compared to control. With these results, we confirm cdECM as a promising biomaterial for adipose tissue engineering.

scholarly journals Osteoblast-Derived Paracrine and Juxtacrine Signals Protect Disseminated Breast Cancer Cells from Stress

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1366
Author(s):  
Russell Hughes ◽  
Xinyue Chen ◽  
Natasha Cowley ◽  
Penelope D. Ottewell ◽  
Rhoda J. Hawkins ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Survival ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cells ◽  
Metastatic Breast ◽  
Accessory Cell ◽  
Cancer Cell Survival

Metastatic breast cancer in bone is incurable and there is an urgent need to develop new therapeutic approaches to improve survival. Key to this is understanding the mechanisms governing cancer cell survival and growth in bone, which involves interplay between malignant and accessory cell types. Here, we performed a cellular and molecular comparison of the bone microenvironment in mouse models representing either metastatic indolence or growth, to identify mechanisms regulating cancer cell survival and fate. In vivo, we show that regardless of their fate, breast cancer cells in bone occupy niches rich in osteoblastic cells. As the number of osteoblasts in bone declines, so does the ability to sustain large numbers of breast cancer cells and support metastatic outgrowth. In vitro, osteoblasts protected breast cancer cells from death induced by cell stress and signaling via gap junctions was found to provide important juxtacrine protective mechanisms between osteoblasts and both MDA-MB-231 (TNBC) and MCF7 (ER+) breast cancer cells. Combined with mathematical modelling, these findings indicate that the fate of DTCs is not controlled through the association with specific vessel subtypes. Instead, numbers of osteoblasts dictate availability of protective niches which breast cancer cells can colonize prior to stimulation of metastatic outgrowth.

scholarly journals A Method for Measurement of Drug Sensitivity of Myeloma Cells Co-Cultured with Bone Marrow Stromal Cells

2013 ◽  
Vol 18 (6) ◽  
pp. 637-646 ◽  
Author(s):  
Kristine Misund ◽  
Katarzyna A. Baranowska ◽  
Toril Holien ◽  
Christoph Rampa ◽  
Dionne C. G. Klein ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Survival ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Large Scale ◽  
Stromal Cell ◽  
Marrow Stromal Cells ◽  
Cell Nuclei ◽  
Myeloma Cells

The tumor microenvironment can profoundly affect tumor cell survival as well as alter antitumor drug activity. However, conventional anticancer drug screening typically is performed in the absence of stromal cells. Here, we analyzed survival of myeloma cells co-cultured with bone marrow stromal cells (BMSC) using an automated fluorescence microscope platform, ScanR. By staining the cell nuclei with DRAQ5, we could distinguish between BMSC and myeloma cells, based on their staining intensity and nuclear shape. Using the apoptotic marker YO-PRO-1, the effects of drug treatment on the viability of the myeloma cells in the presence of stromal cells could be measured. The method does not require cell staining before incubation with drugs, and less than 5000 cells are required per condition. The method can be used for large-scale screening of anticancer drugs on primary myeloma cells. This study shows the importance of stromal cell support for primary myeloma cell survival in vitro, as half of the cell samples had a marked increase in their viability when cultured in the presence of BMSC. Stromal cell–induced protection against common myeloma drugs is also observed with this method.

scholarly journals Transforming Growth Factor β1 (TGF-β1) Promotes Endothelial Cell Survival during In Vitro Angiogenesis via an Autocrine Mechanism Implicating TGF-α Signaling

2001 ◽  
Vol 21 (21) ◽  
pp. 7218-7230 ◽  
Author(s):  
Francesc Viñals ◽  
Jacques Pouysségur
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Cell Survival ◽  
Network Formation ◽  
Egf Receptor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
In Vitro Angiogenesis ◽  
Tgf Β1

ABSTRACT Mouse capillary endothelial cells (1G11 cell line) embedded in type I collagen gels undergo in vitro angiogenesis. Cells rapidly reorganize and form capillary-like structures when stimulated with serum. Transforming growth factor β1 (TGF-β1) alone can substitute for serum and induce cell survival and tubular network formation. This TGF-β1-mediated angiogenic activity depends on phosphatidylinositol 3-kinase (PI3K) and p42/p44 mitogen-activated protein kinase (MAPK) signaling. We showed that specific inhibitors of either pathway (wortmannin, LY-294002, and PD-98059) all suppressed TGF-β1-induced angiogenesis mainly by compromising cell survival. We established that TGF-β1 stimulated the expression of TGF-α mRNA and protein, the tyrosine phosphorylation of a 170-kDa membrane protein representing the epidermal growth factor (EGF) receptor, and the delayed activation of PI3K/Akt and p42/p44 MAPK. Moreover, we showed that all these TGF-β1-mediated signaling events, including tubular network formation, were suppressed by incubating TGF-β1-stimulated endothelial cells with a soluble form of an EGF receptor (ErbB-1) or tyrphostin AG1478, a specific blocker of EGF receptor tyrosine kinase. Finally, addition of TGF-α alone poorly stimulated angiogenesis; however, by reducing cell death, it strongly potentiated the action of TGF-β1. We therefore propose that TGF-β1 promotes angiogenesis at least in part via the autocrine secretion of TGF-α, a cell survival growth factor, activating PI3K/Akt and p42/p44 MAPK.

scholarly journals Real-Time Intraoperative MRI Intracerebral Delivery of Induced Pluripotent Stem Cell-Derived Neurons

2017 ◽  
Vol 26 (4) ◽  
pp. 613-624 ◽  
Author(s):  
Scott C. Vermilyea ◽  
Jianfeng Lu ◽  
Miles Olsen ◽  
Scott Guthrie ◽  
Yunlong Tao ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Survival ◽  
Real Time ◽  
Pluripotent Stem Cell ◽  
Viral Vector ◽  
Induced Pluripotent Stem Cell ◽  
Cell Delivery ◽  
Intracerebral Injection ◽  
Induced Pluripotent

Induced pluripotent stem cell (iPSC)-derived neurons represent an opportunity for cell replacement strategies for neurodegenerative disorders such as Parkinson's disease (PD). Improvement in cell graft targeting, distribution, and density can be key for disease modification. We have previously developed a trajectory guide system for real-time intraoperative magnetic resonance imaging (RT-IMRI) delivery of infusates, such as viral vector suspensions for gene therapy strategies. Intracerebral delivery of iPSC-derived neurons presents different challenges than viral vectors, including limited cell survival if cells are kept at room temperature for prolonged periods of time, precipitation and aggregation of cells in the cannula, and obstruction during injection, which must be solved for successful application of this delivery approach. To develop procedures suitable for RT-IMRI cell delivery, we first performed in vitro studies to tailor the delivery hardware (e.g., cannula) and defined a range of parameters to be applied (e.g., maximal time span allowable between cell loading in the system and intracerebral injection) to ensure cell survival. Then we performed an in vivo study to evaluate the feasibility of applying the system to nonhuman primates. Our results demonstrate that the RT-IMRI delivery system provides valuable guidance, monitoring, and visualization during intracerebral cell delivery that are compatible with cell survival.

Complimentary action: C1q increases ganglion cell survival in an in vitro model of retinal degeneration

2016 ◽  
Vol 298 ◽  
pp. 117-129 ◽  
Author(s):  
Linnéa Taylor ◽  
Karin Arnér ◽  
Anna M. Blom ◽  
Fredrik Ghosh
Keyword(s):  
Ganglion Cell ◽  
Cell Survival ◽  
Retinal Degeneration ◽  
In Vitro Model ◽  
Vitro Model
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