Abstract

Dedifferentiated liposarcoma (DDLPS) is a highly malignant sarcoma characterized by the co-amplification of MDM2 and CDK4. Although systemic chemotherapy is recommended for unresectable or metastatic cases, DDLPS is insensitive to conventional chemotherapy, leading to an unfavorable prognosis. Therefore, novel treatment methods are urgently required. Patient-derived cell lines are essential in preclinical studies. Recently, large-scale screening studies using a number of cell lines have been actively conducted for the development of new therapeutic drugs. However, the DDLPS cell line cannot be obtained from public cell banks owing to its rarity, hindering screening studies. As such, novel DDLPS cell lines need to be established. Accordingly, this study aimed to establish a novel DDLPS cell line from surgical specimens. The cell line was named NCC-DDLPS4-C1. NCC-DDLPS4-C1 cells retained copy number alterations corresponding to the original tumors. Further, the cells demonstrated constant growth, spheroid formation, and equivalent invasiveness to MG63 osteosarcoma cells. We also conducted drug screening and integrated the results with those of the previously reported DDLPS cell lines. Consequently, we identified the histone deacetylase inhibitor romidepsin as a novel candidate drug. In conclusion, the NCC-DDLPS4-C1 cell line is a useful tool for the basic study of DDLPS.

Highlights

  • Dedifferentiated liposarcoma (DDLPS) is a typical non-lipogenic sarcoma that develops from an atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDLPS) [1].DDLPS usually affects elderly patients, and the most common site is the retroperitoneum, followed by the extremities [1,2,3,4]

  • The NCC-DDLPS4-C1 cell line was authenticated by analyzing the STR at 10 loci (Table 1, Figure S1)

  • 93.3%, as calculated by the Tanabe formula [35]. This score met the 80% threshold [36], guaranteeing that the NCC-DDLPS4-C1 cell line was established from the original tumor

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Summary

Introduction

Dedifferentiated liposarcoma (DDLPS) is a typical non-lipogenic sarcoma that develops from an atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDLPS) [1]. DDLPS usually affects elderly patients, and the most common site is the retroperitoneum, followed by the extremities [1,2,3,4]. DDLPS is characterized by the amplification of MDM2 and CDK4 at 12q13-15 and by ALT/WDLPS [1,2,4,5,6]. Multiple gene amplifications at 12q13-15, such as those of HMGA2, TSPAN31, and CPM, have been identified in DDLPS [2,4,5,6,7]. Unlike ALT/WDLPS, DDLPS has a highly aggressive potential and has an unfavorable prognosis

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