Development and characterization of a cancer cachexia model employing a rare human duodenal neuroendocrine carcinoma-originating cell line.
IL-8
angiogenesis
cancer cachexia
duodenal neuroendocrine carcinoma
orthotopic animal model
Journal
Oncotarget
ISSN: 1949-2553
Titre abrégé: Oncotarget
Pays: United States
ID NLM: 101532965
Informations de publication
Date de publication:
29 Mar 2019
29 Mar 2019
Historique:
received:
18
12
2018
accepted:
15
02
2019
entrez:
10
5
2019
pubmed:
10
5
2019
medline:
10
5
2019
Statut:
epublish
Résumé
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 TCC-NECT-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.
Identifiants
pubmed: 31069007
doi: 10.18632/oncotarget.26764
pii: 26764
pmc: PMC6497432
doi:
Types de publication
Journal Article
Langues
eng
Pagination
2435-2450Déclaration de conflit d'intérêts
CONFLICTS OF INTEREST The authors declare no potential conflicts of interest.
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