Mandibular undifferentiated pleomorphic sarcoma: Molecular analysis of a primary cell population.
MMPs
NOTCH
oral cancer
primary cells
sarcoma
Journal
Clinical and experimental dental research
ISSN: 2057-4347
Titre abrégé: Clin Exp Dent Res
Pays: United States
ID NLM: 101692332
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
15
01
2020
revised:
22
04
2020
accepted:
29
04
2020
pubmed:
12
7
2020
medline:
24
8
2021
entrez:
12
7
2020
Statut:
ppublish
Résumé
Undifferentiated pleomorphic sarcomas are one of the most common subtypes of soft tissue sarcomas. These are aggressive mesenchymal tumors and are devoid of the major known biomarkers except vimentin. Our objective was to establish and characterize a primary cell population from a mandibular UPS specimen. The tumor was surgically removed from the right mandible of a 24-year-old male with IRB approved signed consent. Tumor was dissected, cultured ex vivo, and a cell population, MUPS-1, were isolated from outgrowths. Gene and protein expression profiles of both the primary tumor and the derived there from cells were obtained by quantitative RT-PCR and immunohistochemistry and included markers of epithelial, endothelial, and mesenchymal differentiation. To better define potential biomarkers, MUPS-1 cells were additionally characterized by RNA sequencing analysis. Pathological analysis of primary tumor tissue revealed a sarcoma demonstrating multiple pathways of differentiation simultaneously with myxoid, fibrous, and osseous tissue. The isolated cells had a spindle cell-like morphology, were maintained in culture for greater than 20 passages, and formed colonies in soft agar indicating tumorigenicity. The cells, similar to the primary tumor, were strongly positive for vimentin and moderately expressed alkaline phosphatase. RNA-seq analysis revealed the tumor over-expressed several genes compared to normal tissue, including components of the Notch signaling pathway, NOTCH3 and JAG1. We have successfully established an undifferentiated pleomorphic sarcoma cell population, which will provide a valuable resource for studying fundamental processes and potentially serving as a platform for exploring therapeutic strategies for sarcomas.
Sections du résumé
BACKGROUND
Undifferentiated pleomorphic sarcomas are one of the most common subtypes of soft tissue sarcomas. These are aggressive mesenchymal tumors and are devoid of the major known biomarkers except vimentin. Our objective was to establish and characterize a primary cell population from a mandibular UPS specimen.
METHODS
The tumor was surgically removed from the right mandible of a 24-year-old male with IRB approved signed consent. Tumor was dissected, cultured ex vivo, and a cell population, MUPS-1, were isolated from outgrowths. Gene and protein expression profiles of both the primary tumor and the derived there from cells were obtained by quantitative RT-PCR and immunohistochemistry and included markers of epithelial, endothelial, and mesenchymal differentiation. To better define potential biomarkers, MUPS-1 cells were additionally characterized by RNA sequencing analysis.
RESULTS
Pathological analysis of primary tumor tissue revealed a sarcoma demonstrating multiple pathways of differentiation simultaneously with myxoid, fibrous, and osseous tissue. The isolated cells had a spindle cell-like morphology, were maintained in culture for greater than 20 passages, and formed colonies in soft agar indicating tumorigenicity. The cells, similar to the primary tumor, were strongly positive for vimentin and moderately expressed alkaline phosphatase. RNA-seq analysis revealed the tumor over-expressed several genes compared to normal tissue, including components of the Notch signaling pathway, NOTCH3 and JAG1.
CONCLUSIONS
We have successfully established an undifferentiated pleomorphic sarcoma cell population, which will provide a valuable resource for studying fundamental processes and potentially serving as a platform for exploring therapeutic strategies for sarcomas.
Identifiants
pubmed: 32652895
doi: 10.1002/cre2.301
pmc: PMC7545231
doi:
Substances chimiques
Biomarkers, Tumor
0
Types de publication
Case Reports
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
495-505Subventions
Organisme : NIDCR NIH HHS
ID : K99 DE023826
Pays : United States
Organisme : NIDCR NIH HHS
ID : R00 DE023826
Pays : United States
Organisme : NIDCR NIH HHS
ID : T90 DE022736
Pays : United States
Informations de copyright
© 2020 The Authors. Clinical and Experimental Dental Research published by John Wiley & Sons Ltd.
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