Summary

In Vitro Cell Dev Biol Anim. 2019 Jan;55(1):62-73. doi: 10.1007/s11626-018-0305-z. Epub 2018 Nov 8.

Establishment of novel patient-derived models of dermatofibrosarcoma protuberans: two cell lines, NCC-DFSP1-C1 and NCC-DFSP2-C1.

Abstract:

Dermatofibrosarcoma protuberans (DFSP) is a common type of dermal sarcoma, characterized by the presence of the unique collagen type I alpha 1 chain (COL1A1)-PDGFB translocation, which causes constitutive activation of the platelet-derived growth factor β (PDGFB) signaling pathway. Patients with DFSP exhibit frequent local recurrence, and novel therapeutic approaches are required to achieve better clinical outcomes. Patient-derived cancer cell lines are essential in the preclinical research. Here, we established novel patient-derived DFSP cell lines from two patients with DFSP and designated these cell lines NCC-DFSP1-C1 and NCC-DFSP2-C1. Tumors of the two patients with DFSP had COL1A1-PDGFB translocations with distinct COL1A1 breakpoints, e.g., in exons 33 and 15, and the translocations were preserved in the established cell lines. NCC-DFSP1-C1 and NCC-DFSP2-C1 cells exhibited similar morphology and limited capability of proliferation in vitro, forming spheroids when seeded on low-attachment tissue culture plates. In contrast, NCC-DFSP1-C1 cells had considerably higher invasive capability than NCC-DFSP2-C1 cells. Overall proteome contents were similar between NCC-DFSP1-C1 and NCC-DFSP2-C1 cells. Notably, in vitro screening studies identified anticancer drugs that showed antiproliferative effects at considerably low concentrations in the DFSP cell lines. Bortezomib, mitoxantrone, ponatinib, and romidepsin were more cytotoxic to NCC-DFSP1-C1 cells than to NCC-DFSP2-C1 cells. These cell lines will be useful tools for developing novel therapeutic strategies to treat DFSP.

日本語要旨:

PMID:  30411273

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