Establishment and characterization of NCC-MRT1-C1: a novel cell line of malignant rhabdoid tumor.

Malignant rhabdoid tumor (MRT) is a sarcoma histologically characterized by rhabdoid cells and genetically characterized by loss of function of the chromatin remodeling complex SWI/SNF induced by SMARCB1 gene deficiency. MRT mainly occurs in children, may arise in various locations, but is predominantly in the central nervous system (CNS) and kidney. Although MRT exhibits poor prognosis, standard treatment has not yet been established due to its extreme rarity. Patient-derived cancer cell lines are critical tools for basic and pre-clinical research in the development of chemotherapy. However, none of the MRT cell lines was derived from adult patients, and only one cell line was derived from the MRT of a soft tissue, despite the clinical behavior of MRT varying according to patient age and anatomic site. Herein, we reported the first cell line of MRT isolated from the soft tissue of an adult patient and named it NCC-MRT1-C1. NCC-MRT1-C1 cells showed a biallelic loss of the SMARCB1 gene. NCC-MRT1-C1 cells demonstrated rapid proliferation, spheroid formation, invasion capability in vitro, and tumorigenesis in nude mice. Screening of antitumor agents in NCC-MRT1-C1 cells resulted in the identification of six effective drugs. In conclusion, we report the first MRT cell line from the soft tissue of an adult patient. We believe that NCC-MRT1-C1 is a useful tool for developing novel chemotherapies for MRT.

Establishment and characterization of NCC-GCTB5-C1: a novel cell line of giant cell tumor of bone.

Giant cell tumor of bone (GCTB), is a rare intermediate malignant bone tumor with high local infiltrative ability, and is genetically characterized by mutation in the H3-3A gene. Standard treatment is curative surgical tumor resection. GCTB demonstrates both local recurrence and pulmonary metastasis after surgical treatment, and effective systematic chemotherapy is yet to be established. Therefore, development of novel chemotherapies for GCTB is necessary. Although patient-derived tumor cell lines are potent tools for preclinical research, 15 GCTB cell lines have been reported to date, and only four are publicly available. Thus, this study aimed to establish and characterize a novel GCTB cell line for preclinical studies on GCTB. Herein, we described the establishment of a cell line, NCC-GCTB5-C1, from the primary tumor tissue of a patient with GCTB. NCC-GCTB5-C1 was shown to harbor a mutation in the H3-3A gene, which is typical of GCTB; thus, it has useful properties for in vitro studies. We conducted the largest integrated screening analysis of 214 antitumor agents using NCC-GCTB5-C1 along with four GCTB cell lines. Romidepsin (a histone deacetylase inhibitor), camptothecin, and actinomycin D (topoisomerase inhibitors) demonstrated remarkable antitumor effects, suggesting that these antitumor agents are potential therapeutic candidates for GCTB treatment. Therefore, the NCC-GCTB5-C1 cell line could potentially contribute to the elucidation of GCTB pathogenesis and the development of novel GCTB treatments.