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建立并鉴定新型去分化脂肪肉瘤患者来源细胞系 NCC-DDLPS6-C1。

Establishment and characterization of a novel patient-derived cell line of dedifferentiated liposarcoma, NCC-DDLPS6-C1.

机构信息

Division of Rare Cancer Research, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.

Division of Musculoskeletal Oncology and Orthopaedics Surgery, Tochigi Cancer Center, 4-9-13 Yohnan, Utsunomiya, Tochigi, 320-0834, Japan.

出版信息

Hum Cell. 2022 Jul;35(4):1270-1278. doi: 10.1007/s13577-022-00710-8. Epub 2022 May 23.

DOI:10.1007/s13577-022-00710-8
PMID:35604485
Abstract

Dedifferentiated liposarcoma (DDLPS) is morphologically characterized by well-differentiated liposarcomas associated with high-grade non-lipogenic sarcoma and molecularly characterized by the coamplification of MDM2 and CDK4(12q14-15). DDLPS is highly aggressive, and effective systemic chemotherapy has not been developed yet. In this study, we established a novel DDLPS cell line, NCC-DDLPS6-C1, as a potential tool for the development of novel therapies. NCC-DDLPS6-C1 cells were established from surgically resected tumor tissues of a patient with DDLPS. Amplification and overexpression of MDM2 and CDK4 were observed in NCC-DDLPS6-C1 cells. NCC-DDLPS6-C1 cells proliferated rapidly, invaded aggressively, and formed spheroids. Moreover, NCC-DDLPS6-C1 cells formed tumors in mice. These observations suggested that the malignant potentials that may reflect the original features of DDLPS were retained in the NCC-DDLPS6-C1. Anticancer drugs that significantly reduced the proliferation of NCC-DDLPS6-C1 cells were identified by drug library screening. Thus, NCC-DDLPS6-C1 may recapitulate the original genotypes and phenotypes, and we conclude that the NCC-DDLPS6-C1 cell line is a useful resource for the study of DDLPS.

摘要

去分化脂肪肉瘤(DDLPS)在形态学上的特征是存在高分化脂肪肉瘤,同时伴有高级非脂肪性肉瘤,在分子水平上表现为 MDM2 和 CDK4(12q14-15)的共扩增。DDLPS 具有高度侵袭性,目前尚未开发出有效的系统化疗方法。在本研究中,我们建立了一种新型的 DDLPS 细胞系 NCC-DDLPS6-C1,作为开发新型治疗方法的潜在工具。NCC-DDLPS6-C1 细胞是从一名 DDLPS 患者的手术切除肿瘤组织中建立的。在 NCC-DDLPS6-C1 细胞中观察到 MDM2 和 CDK4 的扩增和过表达。NCC-DDLPS6-C1 细胞增殖迅速,侵袭性强,并形成球体。此外,NCC-DDLPS6-C1 细胞在小鼠体内形成肿瘤。这些观察结果表明,NCC-DDLPS6-C1 保留了可能反映 DDLPS 原始特征的恶性潜能。通过药物文库筛选鉴定出能显著抑制 NCC-DDLPS6-C1 细胞增殖的抗癌药物。因此,NCC-DDLPS6-C1 可能重现了原始的基因型和表型,我们得出结论,NCC-DDLPS6-C1 细胞系是研究 DDLPS 的有用资源。

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