Mandibular undifferentiated pleomorphic sarcoma: Molecular analysis of a primary cell population
Abstract 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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2020-10-01
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| Series: | Clinical and Experimental Dental Research |
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| Online Access: | https://doi.org/10.1002/cre2.301 |
| _version_ | 1828822378402021376 |
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| author | Hope M. Amm Patricia DeVilliers Ambika R. Srivastava Marina G. Diniz Gene P. Siegal Mary MacDougall |
| author_facet | Hope M. Amm Patricia DeVilliers Ambika R. Srivastava Marina G. Diniz Gene P. Siegal Mary MacDougall |
| author_sort | Hope M. Amm |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-12T13:12:44Z |
| format | Article |
| id | doaj.art-00262239d7cb4c7b8bc19bc7fd98308e |
| institution | Directory Open Access Journal |
| issn | 2057-4347 |
| language | English |
| last_indexed | 2024-12-12T13:12:44Z |
| publishDate | 2020-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical and Experimental Dental Research |
| spelling | doaj.art-00262239d7cb4c7b8bc19bc7fd98308e2022-12-22T00:23:29ZengWileyClinical and Experimental Dental Research2057-43472020-10-016549550510.1002/cre2.301Mandibular undifferentiated pleomorphic sarcoma: Molecular analysis of a primary cell populationHope M. Amm0Patricia DeVilliers1Ambika R. Srivastava2Marina G. Diniz3Gene P. Siegal4Mary MacDougall5Oral and Maxillofacial Surgery University of Alabama at Birmingham Birmingham Alabama USADepartment of Pathology University of Alabama at Birmingham Birmingham Alabama USADepartment of Biomedical Engineering University of Alabama at Birmingham Birmingham Alabama USADepartment of Pathology and Oral Surgery and Pathology Universidade Federal de Minas Gerais Belo Horizonte BrazilDepartment of Pathology University of Alabama at Birmingham Birmingham Alabama USAOral and Maxillofacial Surgery University of Alabama at Birmingham Birmingham Alabama USAAbstract 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.https://doi.org/10.1002/cre2.301MMPsNOTCHoral cancerprimary cellssarcoma |
| spellingShingle | Hope M. Amm Patricia DeVilliers Ambika R. Srivastava Marina G. Diniz Gene P. Siegal Mary MacDougall Mandibular undifferentiated pleomorphic sarcoma: Molecular analysis of a primary cell population Clinical and Experimental Dental Research MMPs NOTCH oral cancer primary cells sarcoma |
| title | Mandibular undifferentiated pleomorphic sarcoma: Molecular analysis of a primary cell population |
| title_full | Mandibular undifferentiated pleomorphic sarcoma: Molecular analysis of a primary cell population |
| title_fullStr | Mandibular undifferentiated pleomorphic sarcoma: Molecular analysis of a primary cell population |
| title_full_unstemmed | Mandibular undifferentiated pleomorphic sarcoma: Molecular analysis of a primary cell population |
| title_short | Mandibular undifferentiated pleomorphic sarcoma: Molecular analysis of a primary cell population |
| title_sort | mandibular undifferentiated pleomorphic sarcoma molecular analysis of a primary cell population |
| topic | MMPs NOTCH oral cancer primary cells sarcoma |
| url | https://doi.org/10.1002/cre2.301 |
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