Explant culture of sarcoma patients' tissue

Muff, Roman; Botter, Sander M.; Husmann, Knut; Tchinda, Joëlle; Selvam, Philomina; Seeli-Maduz, Franziska; Fuchs, Bruno

doi:10.1038/labinvest.2016.49

Cited by 5 publications

(5 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Ewing cells were authenticated by STR profiling in 2016/05. Primary Ewing cell lines were characterized by karyotyping at the diagnostic laboratory of the Children´s Hospital Zurich, Switzerland and described before 55 . The use of primary cells did not required ethical approval.…”

Section: Methodsmentioning

confidence: 99%

USP19 deubiquitinates EWS-FLI1 to regulate Ewing sarcoma growth

Gierisch

Pedot

Walser

et al. 2019

Sci Rep

View full text Add to dashboard Cite

Ewing sarcoma is the second most common pediatric bone and soft tissue tumor presenting with an aggressive behavior and prevalence to metastasize. The diagnostic translocation t(22;11)(q24;12) leads to expression of the chimeric oncoprotein EWS-FLI1 which is uniquely expressed in all tumor cells and maintains their survival. Constant EWS-FLI1 protein turnover is regulated by the ubiquitin proteasome system. Here, we now identified ubiquitin specific protease 19 (USP19) as a regulator of EWS-FLI1 stability using an siRNA based screening approach. Depletion of USP19 resulted in diminished EWS-FLI1 protein levels and, vice versa, upregulation of active USP19 stabilized the fusion protein. Importantly, stabilization appears to be specific for the fusion protein as it could not be observed neither for EWSR1 nor for FLI1 wild type proteins even though USP19 binds to the N-terminal EWS region to regulate deubiquitination of both EWS-FLI1 and EWSR1. Further, stable shUSP19 depletion resulted in decreased cell growth and diminished colony forming capacity in vitro, and significantly delayed tumor growth in vivo. Our findings not only provide novel insights into the importance of the N-terminal EWSR1 domain for regulation of fusion protein stability, but also indicate that inhibition of deubiquitinating enzyme(s) might constitute a novel therapeutic strategy in treatment of Ewing sarcoma.

show abstract

Section: Methodsmentioning

confidence: 99%

USP19 deubiquitinates EWS-FLI1 to regulate Ewing sarcoma growth

Gierisch

Pedot

Walser

et al. 2019

Sci Rep

View full text Add to dashboard Cite

show abstract

“…In fact, the success rate in establishing cultures derived from patient samples is 82% in bone tumors and 68% in STS [66]. There are different techniques for the isolation of CSCs based on their unique characteristics, including drug resistance, dye explosion or SP assay, separation using surface markers with FACS or MACS, or ALDH activity.…”

Section: Discussionmentioning

confidence: 99%

Cancer Stem Cells in Sarcomas: In Vitro Isolation and Role as Prognostic Markers: A Systematic Review

Chico

Mesas

Doello

et al. 2023

Cancers

View full text Add to dashboard Cite

Sarcomas are a diverse group of neoplasms with an incidence rate of 15% of childhood cancers. They exhibit a high tendency to develop early metastases and are often resistant to available treatments, resulting in poor prognosis and survival. In this context, cancer stem cells (CSCs) have been implicated in recurrence, metastasis, and drug resistance, making the search for diagnostic and prognostic biomarkers of the disease crucial. The objective of this systematic review was to analyze the expression of CSC biomarkers both after isolation from in vitro cell lines and from the complete cell population of patient tumor samples. A total of 228 publications from January 2011 to June 2021 was retrieved from different databases, of which 35 articles were included for analysis. The studies demonstrated significant heterogeneity in both the markers detected and the CSC isolation techniques used. ALDH was identified as a common marker in various types of sarcomas. In conclusion, the identification of CSC markers in sarcomas may facilitate the development of personalized medicine and improve treatment outcomes.

show abstract

“…The cell lines were authenticated by short tandem repeat DNA profiling (Microsynth, Balgach, Switzerland) with a PowerPlex16HS system (Promega, Madison, WI, USA; DC2101) and by comparison with the German Collection of Microorganisms and Cell Cultures database (https://www.dsmz.de/). Primary cell lines were generated from resections of benign chondrogenic tumors collected at Balgrist University Hospital and cultured as described . One randomly selected enchondroma‐derived (#4) and two osteochondroma‐derived (#5, #10) cell lines were used.…”

Section: Methodsmentioning

confidence: 99%

“…Primary cell lines were generated from resections of benign chondrogenic tumors collected at Balgrist University Hospital and cultured as described. (16) One randomly selected enchondroma-derived (#4) and two osteochondroma-derived (#5, #10) cell lines were used.…”

Section: Cell Culturementioning

confidence: 99%

The miR-143/145 Cluster, a Novel Diagnostic Biomarker in Chondrosarcoma, Acts as a Tumor Suppressor and Directly Inhibits Fascin-1

Urdínez

Boro

Mazumdar

et al. 2020

Journal of Bone and Mineral Research

Self Cite

View full text Add to dashboard Cite

Chondrosarcoma is the second most frequent bone sarcoma. Due to the inherent chemotherapy and radiotherapy resistance and absence of known therapeutic targets, clinical management is limited to surgical resection. Consequently, patients with advanced disease face a poor prognosis. Hence, elucidating regulatory networks governing chondrosarcoma pathogenesis is vital for development of effective therapeutic strategies. Here, miRNA and mRNA next generation sequencing of different subtypes of human chondrogenic tumors in combination with in silico bioinformatics tools were performed with the aim to identify key molecular factors. We identified miR‐143/145 cluster levels to inversely correlate with tumor grade. This deregulation was echoed in the miRNA plasma levels of patients and we provided the first evidence that circulating miR‐145 is a potential noninvasive diagnostic biomarker and can be valuable as an indicator to improve the currently challenging diagnosis of cartilaginous bone tumors. Additionally, artificial upregulation of both miRNAs impelled a potent tumor suppressor effect in vitro and in vivo in an orthotopic xenograft mouse model. A combined in silico/sequencing approach revealed FSCN1 as a direct target of miR‐143/145, and its depletion phenotypically resembled miR‐143/145 upregulation in vitro. Last, FSCN1 is a malignancy‐promoting factor associated with aggressive chondrosarcoma progression. Our findings underscore miR‐143/145/FSCN1 as important players in chondrosarcoma and may potentially open new avenues for specific therapeutic intervention options. © 2020 American Society for Bone and Mineral Research.

show abstract

Explant culture of sarcoma patients' tissue

Cited by 5 publications

References 39 publications

USP19 deubiquitinates EWS-FLI1 to regulate Ewing sarcoma growth

USP19 deubiquitinates EWS-FLI1 to regulate Ewing sarcoma growth

Cancer Stem Cells in Sarcomas: In Vitro Isolation and Role as Prognostic Markers: A Systematic Review

The miR-143/145 Cluster, a Novel Diagnostic Biomarker in Chondrosarcoma, Acts as a Tumor Suppressor and Directly Inhibits Fascin-1

Contact Info

Product

Resources

About