Endothelins may modulate invasion and proliferation of Ewing's sarcoma and neuroblastoma

2002 ◽  
Vol 103 (s2002) ◽  
pp. 322S-326S ◽  
Author(s):  
Paul BERRY ◽  
Susan BURCHILL
Keyword(s):  
Cell Proliferation ◽  
Reverse Transcriptase ◽  
Receptor Antagonist ◽  
Disease Progression ◽  
Cell Lines ◽  
Ewing’S Sarcoma ◽  
Ewing's Sarcoma ◽  
Neutralizing Antibody ◽  
Es Cell ◽  
Receptor Mrna

Tumours of the Ewing's sarcoma (ES) family and neuroblastoma (NBL) were examined by reverse transcriptase-PCR for expression of mRNA for endothelin (ET) receptors ET-A and ET-B, and the ligands ET-1, ET-2 and ET-3. The effect of ET-1, ET-3, an ET-1-neutralizing antibody and ET-A receptor antagonist BQ-123 on cell proliferation was examined using an ELISA. Loss of ET-B receptor mRNA occurred in 57% of ES and 42% of NBL tumours. This appeared to be associated with the presence of metastatic disease and disease progression. ET-A receptor mRNA was expressed in all ES and 85% of NBL tumours, and in all ES and NBL cell lines examined. All ET ligands were detected in NBL cell lines, but only ET-1 and ET-2 were expressed in ES cell lines. Treatment of ES and NBL cells with ET-1 increased proliferation, but ET-3 had no effect. Incubation of ES and NBL cells with an ET-1-neutralizing antibody or BQ-123 decreased proliferation. The ET-3 ligand and ET-B receptor may be associated with migration and metastasis of ES and NBL, whereas ET-1 (acting through the ET-A receptor) may regulate their proliferation.

scholarly journals PDX-Derived Ewing’s Sarcoma Cells Retain High Viability and Disease Phenotype in Alginate Encapsulated Spheroid Cultures

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 879
Author(s):  
Giacomo Domenici ◽  
Rodrigo Eduardo ◽  
Helena Castillo-Ecija ◽  
Gorka Orive ◽  
Ángel Montero Carcaboso ◽  
...  
Keyword(s):  
Cell Culture ◽  
Cell Lines ◽  
Drug Sensitivity ◽  
Ewing’S Sarcoma ◽  
Ewing's Sarcoma ◽  
3D Cell Culture ◽  
Suitable Model ◽  
Es Cell ◽  
3D Cultures ◽  
Novel Drugs

Ewing’s Sarcoma (ES) is the second most frequent malignant bone tumour in children and young adults and currently only untargeted chemotherapeutic approaches and surgery are available as treatment, although clinical trials are on-going for recently developed ES-targeted therapies. To study ES pathobiology and develop novel drugs, established cell lines and patient-derived xenografts (PDX) are the most employed experimental models. Nevertheless, the establishment of ES cell lines is difficult and the extensive use of PDX raises economic/ethical concerns. There is a growing consensus regarding the use of 3D cell culture to recapitulate physiological and pathophysiological features of human tissues, including drug sensitivity. Herein, we implemented a 3D cell culture methodology based on encapsulation of PDX-derived ES cell spheroids in alginate and maintenance in agitation-based culture systems. Under these conditions, ES cells displayed high proliferative and metabolic activity, while retaining the typical EWSR1-FLI1 chromosomal translocation. Importantly, 3D cultures presented reduced mouse PDX cell contamination compared to 2D cultures. Finally, we show that these 3D cultures can be employed in drug sensitivity assays, with results similar to those reported for the PDX of origin. In conclusion, this novel 3D cell culture method involving ES-PDX-derived cells is a suitable model to study ES pathobiology and can assist in the development of novel drugs against this disease, complementing PDX studies.

c-kit Receptor Expression in Ewing’s Sarcoma: Lack of Prognostic Value but Therapeutic Targeting Opportunities in Appropriate Conditions

2003 ◽  
Vol 21 (10) ◽  
pp. 1952-1960 ◽  
Author(s):  
Katia Scotlandi ◽  
Maria Cristina Manara ◽  
Rosaria Strammiello ◽  
Lorena Landuzzi ◽  
Stefania Benini ◽  
...  
Keyword(s):  
Growth Inhibition ◽  
Cell Lines ◽  
Ewing’S Sarcoma ◽  
Ewing's Sarcoma ◽  
Receptor Expression ◽  
In Vitro Growth ◽  
Es Cell ◽  
Primary Tumors ◽  
Sti 571

Purpose: Autocrine/paracrine stimulation of c-kit has been recently observed in Ewing’s sarcoma (ES) cell lines. In this study, we tested the prognostic and therapeutic role of the receptor in this tumor. Methods: One hundred one ES tumor biopsies were evaluated for the expression of c-kit by the avidin-biotin-peroxidase procedure. Effectiveness of STI-571 (Gleevec; Novartis, Basel, Switzerland), a selective inhibitor of specific tyrosine kinases, was analyzed with respect to in vitro growth and migration inhibition, as single agent or in combination with doxorubicin. Results: Approximately 30% of patients expressed c-kit in their primary tumors. No significant association between the expression of the receptor and the clinical outcome was observed. In vitro growth of ES cell lines showing high levels of c-kit demonstrated limited inhibition by exposure to STI-571 (10 μmol/L is required to obtain 40% to 50% of growth inhibition). A decrease of stem-cell factor–mediated ES cell migration was also found. The drug acted additively with doxorubicin in inhibiting ES cell growth. Conclusion: The negative prognostic findings and the limited in vitro therapeutic activity of STI-571 indicate that the putative aberrant signaling provided by c-kit overexpression may be dispensable for ES development and unlikely to constitute a critical therapeutic target. Accordingly, the dose of STI-571 required to give a significant ES growth inhibition is much higher than for those tumors in which mutations of c-kit constitute a relevant pathogenetic event. Nevertheless, in the subset of ES patients showing a high level of c-kit expression, the activity of the drug may be exploited in combination with standard therapy.

Chromosome study of Ewing's Sarcoma (ES) cell lines. Consistency of a reciprocal translocation t(11;22)(q24;q12)

1984 ◽  
Vol 12 (1) ◽  
pp. 1-19 ◽  
Author(s):  
Claude Turc-Carel ◽  
Irène Philip ◽  
Marie-Pierre Berger ◽  
Thierry Philip ◽  
Gilbert M. Lenoir
Keyword(s):  
Cell Lines ◽  
Reciprocal Translocation ◽  
Ewing’S Sarcoma ◽  
Ewing's Sarcoma ◽  
Chromosome Study ◽  
Es Cell

scholarly journals Sonic Hedgehog Signature in Pediatric Primary Bone Tumors: Effects of the GLI Antagonist GANT61 on Ewing’s Sarcoma Tumor Growth

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3438
Author(s):  
Mathilde Mullard ◽  
Marie Cadé ◽  
Sarah Morice ◽  
Maryne Dupuy ◽  
Geoffroy Danieau ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Cell Lines ◽  
Sonic Hedgehog ◽  
Bone Tumors ◽  
Ewing’S Sarcoma ◽  
Ewing's Sarcoma ◽  
Es Cells ◽  
Transcriptional Factor ◽  
Es Cell ◽  
Shh Signaling

Osteosarcoma (OS) and Ewing’s sarcoma (ES) are the most common malignant bone tumors in children and adolescents. In many cases, the prognosis remains very poor. The Sonic hedgehog (SHH) signaling pathway, strongly involved in the development of many cancers, regulate transcription via the transcriptional factors Gli1-3. In this context, RNAseq analysis of OS and ES cell lines reveals an increase of some major compounds of the SHH signaling cascade in ES cells, such as the transcriptional factor Gli1. This increase leads to an augmentation of the transcriptional response of Gli1 in ES cell lines, demonstrating a dysregulation of Gli1 signaling in ES cells and thus the rationale for targeting Gli1 in ES. The use of a preclinical model of ES demonstrates that GANT61, an inhibitor of the transcriptional factor Gli1, reduces ES primary tumor growth. In vitro experiments show that GANT61 decreases the viability of ES cell, mainly through its ability to induce caspase-3/7-dependent cell apoptosis. Taken together, these results demonstrates that GANT61 may be a promising therapeutic strategy for inhibiting the progression of primary ES tumors.

scholarly journals Characterization and Drug Resistance Patterns of Ewing's Sarcoma Family Tumor Cell Lines

PLoS ONE ◽  
2013 ◽  
Vol 8 (12) ◽  
pp. e80060 ◽  
Author(s):  
William A. May ◽  
Rita S. Grigoryan ◽  
Nino Keshelava ◽  
Daniel J. Cabral ◽  
Laura L. Christensen ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Tumor Cell ◽  
Cell Lines ◽  
Ewing’S Sarcoma ◽  
Ewing's Sarcoma ◽  
Tumor Cell Lines ◽  
Resistance Patterns

scholarly journals An Innovative Therapeutic Option for the Treatment of Skeletal Sarcomas: Elimination of Osteo- and Ewing’s Sarcoma Cells Using Physical Gas Plasma

2020 ◽  
Vol 21 (12) ◽  
pp. 4460 ◽  
Author(s):  
Josephine M. Jacoby ◽  
Silas Strakeljahn ◽  
Andreas Nitsch ◽  
Sander Bekeschus ◽  
Peter Hinz ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Cell Lines ◽  
Ewing’S Sarcoma ◽  
Ewing's Sarcoma ◽  
Therapeutic Option ◽  
Bone Sarcoma ◽  
Atmospheric Plasma ◽  
Local Surgery ◽  
Release Assay ◽  
Sarcoma Cells

Osteosarcoma and Ewing’s sarcoma are the most common malignant bone tumors. Conventional therapies such as polychemotherapy, local surgery, and radiotherapy improve the clinical outcome for patients. However, they are accompanied by acute and chronic side effects that affect the quality of life of patients, motivating novel research lines on therapeutic options for the treatment of sarcomas. Previous experimental work with physical plasma operated at body temperature (cold atmospheric plasma, CAP) demonstrated anti-oncogenic effects on different cancer cell types. This study investigated the anti-cancer effect of CAP on two bone sarcoma entities, osteosarcoma and Ewing’s sarcoma, which were represented by four cell lines (U2-OS, MNNG/HOS, A673, and RD-ES). A time-dependent anti-proliferative effect of CAP on all cell lines was observed. CAP-induced alterations in cell membrane functionality were detected by performing a fluorescein diacetate (FDA) release assay and an ATP release assay. Additionally, modifications of the cell membrane and modifications in the actin cytoskeleton composition were examined using fluorescence microscopy monitoring dextran-uptake assay and G-/F-actin distribution. Furthermore, the CAP-induced induction of apoptosis was determined by TUNEL and active caspases assays. The observations suggest that a single CAP treatment of bone sarcoma cells may have significant anti-oncogenic effects and thus may be a promising extension to existing applications.

scholarly journals Inhibition of heat shock proteins (HSP) expression by quercetin and differential doxorubicin sensitization in neuroblastoma and Ewing’s sarcoma cell lines

2007 ◽  
Vol 103 (4) ◽  
pp. 1344-1354 ◽  
Author(s):  
Cristina Zanini ◽  
Giuliana Giribaldi ◽  
Giorgia Mandili ◽  
Franco Carta ◽  
Nicoletta Crescenzio ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Proteins ◽  
Cell Lines ◽  
Ewing’S Sarcoma ◽  
Ewing's Sarcoma ◽  
Sarcoma Cell ◽  
Shock Proteins
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