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Establishment and characterization of the third non-functional human pancreatic neuroendocrine tumor cell line.

Authors :
Lou, Xin
Ye, Zeng
Xu, Xiaowu
Jiang, Minglei
Lu, Renquan
Jing, Desheng
Zhang, Wuhu
Gao, Heli
Wang, Fei
Zhang, Yue
Chen, Xuemin
Qin, Yi
Zhuo, Qifeng
Yu, Xianjun
Ji, Shunrong
Source :
Human Cell; Jul2022, Vol. 35 Issue 4, p1248-1261, 14p
Publication Year :
2022

Abstract

The mechanisms of neuroendocrine tumor (NET) were still poorly understood, largely due to the lack of preclinical models of neuroendocrine neoplasms. Herein, we established and characterized SPNE1 cell lines from primary pancreatic NET tissue obtained from a 44-year-old female. Neuroendocrine character of SPNE1 was compared with existing non-functional cell lines BON1 and QGP1, and the results indicated expressions of multiple NET-specific markers in SPNE1 were higher relative to BON1 and QGP1. The growth character measured by Ki67 labeling index, cell cycle analysis, and 3D matrigel spheroid essay indicated that the proliferative rate of SPNE1 was lower than that of BON1 and QGP1. SPNE1 also was characterized with cancer stemness because of the higher proportion of CD44 + and CD117 + subpopulations relative to BON1, whereas it was similar to that of QGP1. Interestingly, SPNE1 highly expressed somatostatin receptors (SSTR2 and SSTR5) and angiogenic factors (VEGF1). SPNE1 had sensitive response to the four clinical treatments including tyrosine kinase inhibitor (TKI), mTOR inhibitors, somatostatin analogs (SSA), chemotherapy, which was similar to the BON1 and QGP1. Subcutaneous transplantations of SPNE1 also present the tumorigenicity, and neuroendocrine marker expression of xenograft tumors resembled the original human NET tissue. Then, we found a total of 8 common mutation in BON1, QGP1 and SPNE1 included CROCC, FAM135A, GPATCH4, CTBP2, FBXL14, HERC2, HYDIN, and PABPC3 using whole-exome sequencing (WES), and more neuroendocrine-related functional processes were enriched based on the private mutation genes in SPNE1, such as neuron migration, insulin secretion, and neuron to neuron synapse. In brief, SPNE1 could be used as a relevant model to study pancreatic NET biology and to develop novel treatment options. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
09147470
Volume :
35
Issue :
4
Database :
Complementary Index
Journal :
Human Cell
Publication Type :
Academic Journal
Accession number :
157613257
Full Text :
https://doi.org/10.1007/s13577-022-00696-3