Varying Opinions on the Authenticity of a Human Midgut Carcinoid Cell Line – Letter

Ellis, Lee M.; Samuel, Shaija; Sceusi, Eric

doi:10.1158/1078-0432.ccr-10-2550

Cited by 25 publications

(21 citation statements)

References 1 publication

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“…A human SI-NET cell line, CNDT2.5, developed from a liver metastasis from a patient diagnosed with primary ileal SI-NET (Van Buren et al 2007), was used in the experiments reported here at cell passages 10-30. These cells expressed neuroendocrine markers and somatostatin receptor 2 and responded to synthetic somatostatin analog (octreotide) treatment (Van Buren et al 2007, Li et al 2012, although skepticism regarding the neuroendocrine authenticity of this cell line has also been raised (Ellis et al 2010). The growth medium for CNDT2.5 was DMEM-F12 complemented with 10% fetal bovine serum (Sigma Aldrich), 1% vitamins, 1% L-glutamine, 1% sodium pyruvate, 1% nonessential amino acids and 1% penicillin-streptomycin (PEST), and the cells were cultured at 37 8C in 5% CO 2 .…”

Section: Tissue Specimensmentioning

confidence: 99%

TCEB3C a putative tumor suppressor gene of small intestinal neuroendocrine tumors

Edfeldt

Ahmad

Åkerström

et al. 2013

Endocrine-Related Cancer

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Small intestinal neuroendocrine tumors (SI-NETs), formerly known as midgut carcinoids, are rare and slow-growing neoplasms. Frequent loss of one copy of chromosome 18 in primary tumors and metastases has been observed. The aim of the study was to investigate a possible role of TCEB3C (Elongin A3), currently the only imprinted gene on chromosome 18, as a tumor suppressor gene in SI-NETs, and whether its expression is epigenetically regulated. Primary tumors, metastases, the human SI-NET cell line CNDT2.5, and two other cell lines were included. Immunohistochemistry, gene copy number determination by PCR, colony formation assay, western blotting, real-time quantitative RT-PCR, RNA interference, and quantitative CpG methylation analysis by pyrosequencing were performed. A large majority of tumors (33/43) showed very low to undetectable Elongin A3 expression and as expected 89% (40/45) displayed one gene copy of TCEB3C. The DNA hypomethylating agent 5-aza-2 0 -deoxycytidine induced TCEB3C expression in CNDT2.5 cells, in primary SI-NET cells prepared directly after surgery, but not in two other cell lines. Also siRNA to DNMT1 and treatment with the general histone methyltransferase inhibitor 3-deazaneplanocin A induced TCEB3C expression in a cell type-specific way. CpG methylation at the TCEB3C promoter was observed in all analyzed tissues and thus not related to expression. Overexpression of TCEB3C resulted in a 50% decrease in clonogenic survival of CNDT2.5 cells, but not of control cells. The results support a putative role of TCEB3C as a tumor suppressor gene in SI-NETs. Epigenetic repression of TCEB3C seems to be tumor cell type-specific and involves both DNA and histone methylation.

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Section: Tissue Specimensmentioning

confidence: 99%

TCEB3C a putative tumor suppressor gene of small intestinal neuroendocrine tumors

Edfeldt

Ahmad

Åkerström

et al. 2013

Endocrine-Related Cancer

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“…CM, LCC-18 and CNDT2.5 (Gueli et al 1987, Lundqvist et al 1991, Van Buren et al 2007. However, the authenticity of CNDT2.5 has been questioned (Ellis et al 2010). There are also GEPNET cell lines derived from transgenic murine rodents, e.g.…”

Section: Introductionmentioning

confidence: 99%

The neuroendocrine phenotype, genomic profile and therapeutic sensitivity of GEPNET cell lines

Hofving¹,

Arvidsson²,

Almobarak³

et al. 2018

Endocrine-Related Cancer

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Experimental models of neuroendocrine tumour disease are scarce, and no comprehensive characterisation of existing gastroenteropancreatic neuroendocrine tumour (GEPNET) cell lines has been reported. In this study, we aimed to define the molecular characteristics and therapeutic sensitivity of these cell lines. We therefore performed immunophenotyping, copy number profiling, whole-exome sequencing and a large-scale inhibitor screening of seven GEPNET cell lines. Four cell lines, GOT1, P-STS, BON-1 and QGP-1, displayed a neuroendocrine phenotype while three others, KRJ-I, L-STS and H-STS, did not. Instead, these three cell lines were identified as lymphoblastoid. Characterisation of remaining authentic GEPNET cell lines by copy number profiling showed that GOT1, among other chromosomal alterations, harboured losses on chromosome 18 encompassing the SMAD4 gene, while P-STS had a loss on 11q. BON-1 had a homozygous loss of CDKN2A and CDKN2B, and QGP-1 harboured amplifications of MDM2 and HMGA2. Whole-exome sequencing revealed both disease-characteristic mutations (e.g. ATRX mutation in QGP-1) and, for patient tumours, rare genetic events (e.g. TP53 mutation in P-STS, BON-1 and QGP-1). A large-scale inhibitor screening showed that cell lines from pancreatic NETs to a greater extent, when compared to small intestinal NETs, were sensitive to inhibitors of MEK. Similarly, neuroendocrine NET cells originating from the small intestine were considerably more sensitive to a group of HDAC inhibitors. Taken together, our results provide a comprehensive characterisation of GEPNET cell lines, demonstrate their relevance as neuroendocrine tumour models and explore their therapeutic sensitivity to a broad range of inhibitors.

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“…[43]. It is, therefore, advised to keep in mind the skepticism of investigators in the field regarding the NE authenticity of this cell line.…”

Section: Gastroenteropancreatic Netsmentioning

confidence: 99%

The Role of Cell Lines in the Study of Neuroendocrine Tumors

2012

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Cell lines originating from neuroendocrine tumors (NETs) represent useful experimental models to assess the control of synthesis and release of different hormones and hormone-like peptides, to evaluate the mechanisms of action of these agents in target tissues at the cellular and subcellular levels, and to study cell proliferation and tumor development, as well as the effect of different drugs on these complex processes. To date, the understanding of NET biology (with regard to their mechanisms of hormone secretion, cell proliferation and metastatic spread) has been hampered by the lack of appropriate animal models or cell lines for their study. In the present review, we aim to summarize the recent in vitro/in vivo data regarding cell lines derived from NETs which are most frequently employed in experimental neuroendocrinology.

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Varying Opinions on the Authenticity of a Human Midgut Carcinoid Cell Line – Letter

Cited by 25 publications

References 1 publication

TCEB3C a putative tumor suppressor gene of small intestinal neuroendocrine tumors

TCEB3C a putative tumor suppressor gene of small intestinal neuroendocrine tumors

The neuroendocrine phenotype, genomic profile and therapeutic sensitivity of GEPNET cell lines

The Role of Cell Lines in the Study of Neuroendocrine Tumors

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