Establishment of a novel cell line from a rare human duodenal poorly differentiated neuroendocrine carcinoma

Kazuyoshi Yanagihara, Takanori Kubo, Keichiro Mihara, Takeshi Kuwata, Atsushi Ochiai, Toshio Seyama, Hiroshi Yokozaki

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

Poorly differentiated neuroendocrine carcinoma of the duodenum (D-NEC) is a rare cancer with poor prognosis. However, a D-NEC cell line has not yet been established to study the disease. We established a cell line, TCC-NECT-2, from the ascites tumor of a 59-year-old male Japanese patient with D-NEC. TCC-NECT-2 was positive for neuroendocrine markers, chromogranin A (CGA), cluster of differentiation 56 (CD56/NCAM), synaptophysin (SYN/p38), and neuron specific enolase (NSE). Cells exhibited retinoblastoma (RB) protein loss. Orthotopic implantation of TCC-NECT-2 cells into nu/nu mice resulted in tumor formation (incidence = 83.3%) with neuroendocrine characteristics, metastasis, and weight loss. BRAFV600E and TP53 mutations and C-MYC gene amplification were also observed in TCC-NECT-2. BRAFV600E-expressing TCC-NECT-2 cells were sensitive to BRAF inhibitor vemurafenib, and especially dabrafenib, in vitro, and were strongly inhibited in a dose-dependent manner. Dabrafenib treatment (30 mg/kg) in a xenograft model for 14 days significantly suppressed tumor growth (percent tumor growth inhibition, TGI% = 48.04). An enhanced therapeutic effect (TGI% = 95.81) was observed on combined treatment of dabrafenib and irinotecan (40 mg/kg). Therefore, TCC-NECT-2, the first reported cell line derived from D-NEC, might serve as a useful model to study the basic biology of D-NEC and translational applications for treatment.

Original languageEnglish
Pages (from-to)36503-36514
Number of pages12
JournalOncotarget
Volume9
Issue number92
DOIs
Publication statusPublished - 01-11-2018
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology

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