Oral and Maxillofacial Surgery, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Clin Exp Dent Res. 2020 Oct;6(5):495-505. doi: 10.1002/cre2.301. Epub 2020 Jul 11.
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.
未分化多形性肉瘤是软组织肉瘤中最常见的亚型之一。这些是侵袭性间叶肿瘤，除波形蛋白外，缺乏主要的已知生物标志物。我们的目的是从下颌 UPS 标本中建立和鉴定原代细胞群体。
肿瘤取自一名 24 岁男性的右侧下颌骨，经 IRB 批准并签署同意书。对肿瘤进行解剖、体外培养，并从生长中分离出一个细胞群体 MUPS-1。通过定量 RT-PCR 和免疫组织化学获得原代肿瘤和由此衍生的细胞的基因和蛋白表达谱，包括上皮、内皮和间充质分化的标志物。为了更好地定义潜在的生物标志物，还通过 RNA 测序分析对 MUPS-1 细胞进行了特征描述。
对原发肿瘤组织的病理分析显示，肉瘤同时具有粘液样、纤维状和骨组织的多种分化途径。分离出的细胞具有梭形细胞样形态，在培养中可维持超过 20 代，并在软琼脂中形成集落，表明具有致瘤性。这些细胞与原代肿瘤一样，对波形蛋白呈强阳性，碱性磷酸酶呈中度表达。RNA-seq 分析显示，与正常组织相比，肿瘤过度表达了几个基因，包括 Notch 信号通路的成分 NOTCH3 和 JAG1。
我们已经成功建立了未分化多形性肉瘤细胞群体，这将为研究基本过程提供有价值的资源，并可能成为探索肉瘤治疗策略的平台。
