Establishment and Characterization of NCC-MFS5-C1: A Novel Patient-Derived Cell Line of Myxofibrosarcoma

Abstract

Myxofibrosarcoma (MFS) is a highly aggressive malignancy with complex karyotypes and a postoperative recurrence tendency, owing to its strong invasiveness. Although systemic chemotherapy is considered in patients with unresectable MFS, the efficacy of conventional chemotherapy is hitherto unclear. Recently, drug screening analysis using a large number of tumor cell lines has been attempted to discover novel therapeutic candidate drugs for common cancers. However, the number of MFS cell lines is extremely small because of its low incidence—this hinders the conduction of screening studies and slows down the development of therapeutic drugs. To overcome this problem, we established a novel MFS cell line, NCC-MFS5-C1, which was shown to harbor typical MFS genetic abnormalities and thus had useful properties for in vitro studies. We conducted the largest integrated screening analysis of 210 drugs using NCC-MFS5-C1 cells along with four MFS cell lines, which we previously reported. Bortezomib (a proteasome inhibitor) and romidepsin (a histone deacetylase inhibitor) showed stronger antitumor effects than the standard drug, doxorubicin. Therefore, the NCC-MFS5-C1 cell line can potentially contribute to elucidating MFS pathogenesis and developing a novel MFS treatment.

Modeling Myxofibrosarcoma: Where Do We Stand and What Is Missing?

“…The so-obtained results show that many of the analyzed drugs do not affect the proliferation of MFS cell lines. Furthermore, these cell lines have different sensitivities to tested drugs [62,63,65,66]. These studies confirm that MFS cells only respond to a limited number of drugs in vitro and are resistant to many others.…”

“…In a recent paper, five MFS cell lines were obtained from different patients, and their invasive properties were compared. The results show that all MFS cell lines have good invasive potential, even with a variable extent [65]. Invasiveness is a key feature of MFS cells, and it is at the base of the recurrence and metastasis of this tumor.…”

“…Despite being such an important feature of MFS, currently, we know very little about the migratory properties of MFS cell lines. Only a few papers have published results on the migration and invasion properties of MFS cells [13,55,59,63,65,66,72]. In some of them, the authors demonstrated that NCC-MFS-1-C1 and NCC-MFS2-C1 are able to invade the matrix using Matrigel invasion chambers [58,62]; moreover, Li et al showed that bortezomib inhibits the invasion potential of NMFH-1 cells [73].…”

“…The most notable advantages of this model are its low production costs and high reproducibility. While some MFS cell lines form spheroids naturally, others need round-bottom and/or low attachment plates in order to do so [58,[62][63][64][65][66].…”

Establishment and characterization of two novel patient-derived cell lines from myxofibrosarcoma: NCC-MFS7-C1 and NCC-MFS8-C1

“…We meticulously characterized the NCC-MFS7-C1 and NCC-MFS8-C1 cell lines and examined their genetic pro les, proliferation rates, spheroid formation capabilities, and invasive behaviors. Additionally, we expanded our investigation to include drug screening across these novel cell lines and six others previously established in our laboratory with the aim of identifying potential therapeutic indications for MFS [15][16][17][18][19][20].…”