Development and characterization of a cancer cachexia model employing a rare human duodenal neuroendocrine carcinomaoriginating cell line

Kazuyoshi Yanagihara, Takanori Kubo, Yuki Iino, Keichiro Mihara, Chie Morimoto, Toshio Seyama, Takeshi Kuwata, Atsushi Ochiai, Hiroshi Yokozaki

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Cancer cachexia interferes with therapy and worsens patients' quality of life. Therefore, for a better understanding of cachexia, we aimed to establish a reliable cell line to develop a cachexia model. We recently established and characterized the TCC-NECT-2 cell line, derived from a Japanese patient with poorly differentiated neuroendocrine carcinoma of the duodenum (D-NEC). Subcutaneous xenograft of TCCNECT- 2 cells in mice resulted in tumor formation, angiogenesis, and 20% incidence of body weight (BW)-loss. Subsequently, we isolated a potent cachexia-inducing subline using stepwise selection and designated as AkuNEC. Orthotopic and s.c. implantation of AkuNEC cells into mice led to diminished BW, anorexia, skeletal muscle atrophy, adipose tissue loss, and decreased locomotor activity at 100% incidence. Additionally, orthotopic implantation of AkuNEC cells resulted in metastasis and angiogenesis. Serum IL-8 overproduction was observed, and levels were positively correlated with BW-loss and reduced adipose tissue and muscle volumes in tumor-bearing mice. However, shRNA knockdown of the IL-8 gene did not suppress tumor growth and cachexia in the AkuNEC model, indicating that IL-8 is not directly involved in cachexia induction. In conclusion, AkuNEC cells may serve as a useful model to study cachexia and D-NEC.

Original languageEnglish
Pages (from-to)2435-2450
Number of pages16
JournalOncotarget
Volume10
Issue number25
DOIs
Publication statusPublished - 29-03-2019

All Science Journal Classification (ASJC) codes

  • Oncology

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