scholarly journals A Comprehensive Molecular Characterization of the Pancreatic Neuroendocrine Tumor Cell Lines BON-1 and QGP-1

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 691 ◽  
Author(s):  
Kim B. Luley ◽  
Shauni B. Biedermann ◽  
Axel Künstner ◽  
Hauke Busch ◽  
Sören Franzenburg ◽  
...  

Experimental models of neuroendocrine tumor disease are scarce, with only a few existing neuroendocrine tumor cell lines of pancreatic origin (panNET). Their molecular characterization has so far focused on the neuroendocrine phenotype and cancer-related mutations, while a transcription-based assessment of their developmental origin and malignant potential is lacking. In this study, we performed immunoblotting and qPCR analysis of neuroendocrine, epithelial, developmental endocrine-related genes as well as next-generation sequencing (NGS) analysis of microRNAs (miRs) on three panNET cell lines, BON-1, QGP-1, and NT-3. All three lines displayed a neuroendocrine and epithelial phenotype; however, while insulinoma-derived NT-3 cells preferentially expressed markers of mature functional pancreatic β-cells (i.e., INS, MAFA), both BON-1 and QGP-1 displayed high expression of genes associated with immature or non-functional β/δ-cells genes (i.e., NEUROG3), or pancreatic endocrine progenitors (i.e., FOXA2). NGS-based identification of miRs in BON-1 and QGP-1 cells revealed the presence of all six members of the miR-17–92 cluster, which have been implicated in β-cell function and differentiation, but also have roles in cancer being both oncogenic or tumor suppressive. Notably, both BON-1 and QGP-1 cells expressed several miRs known to be negatively associated with epithelial–mesenchymal transition, invasion or metastasis. Moreover, both cell lines failed to exhibit migratory activity in vitro. Taken together, NT-3 cells resemble mature functional β-cells, while both BON-1 and QGP-1 are more similar to immature/non-functional pancreatic β/δ-cells or pancreatic endocrine progenitors. Based on the recent identification of three transcriptional subtypes in panNETs, NT-3 cells resemble the “islet/insulinoma tumors” (IT) subtype, while BON-1 and QGP-1 cells were tentatively classified as “metastasis-like/primary” (MLP). Our results provide a comprehensive characterization of three panNET cell lines and demonstrate their relevance as neuroendocrine tumor models.

1993 ◽  
Vol 119 (9) ◽  
pp. 527-532 ◽  
Author(s):  
Brigitte Schott ◽  
Danielle Londos-Gagliardi ◽  
Colette Ries ◽  
Sylvie Huet ◽  
Jacques Robert

2006 ◽  
Vol 11 (8) ◽  
pp. 922-932 ◽  
Author(s):  
Andrea Ivascu ◽  
Manfred Kubbies

Spheroids are widely used in biology because they provide an in vitro 3-dimensional (3D) model to study proliferation, cell death, differentiation, and metabolism of cells in tumors and the response of tumors to radiotherapy and chemotherapy. The methods of generating spheroids are limited by size heterogeneity, long cultivation time, or mechanical accessibility for higher throughput fashion. The authors present a rapid method to generate single spheroids in suspension culture in individual wells. A defined number of cells ranging from 1000 to 20,000 were seeded into wells of poly-HEMA-coated, 96-well, round-or conical-bottom plates in standard medium and centrifuged for 10 min at 1000 g. This procedure generates single spheroids in each well within a 24-h culture time with homogeneous sizes, morphologies, and stratification of proliferating cells in the rim and dying cells in the core region. Because a large number of tumor cell lines form only loose aggregates when cultured in 3D, the authors also performed a screen for medium additives to achieve a switch from aggregate to spheroid morphology. Small quantities of the basement membrane extract Matrigel, added to the culture medium prior to centrifugation, most effectively induced compact spheroid formation. The compact spheroid morphology is evident as early as 24 h after centrifugation in a true suspension culture. Twenty tumor cell lines of different lineages have been used to successfully generate compact, single spheroids with homogenous size in 96-well plates and are easily accessible for subsequent functional analysis.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Christoph Lübbehüsen ◽  
Julian Lüke ◽  
Carolin Seeling ◽  
Kevin Mellert ◽  
Ralf Marienfeld ◽  
...  

1999 ◽  
Vol 44 (3) ◽  
pp. 235-240 ◽  
Author(s):  
Michael J. Kelner ◽  
Trevor C. McMorris ◽  
Mark A. Montoya ◽  
Leita Estes ◽  
Sheldon F. Uglik ◽  
...  

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Wilfredo Hernández ◽  
Juan Paz ◽  
Fernando Carrasco ◽  
Abraham Vaisberg ◽  
Evgenia Spodine ◽  
...  

The palladium(II) bis-chelate complexes of the type [Pd(TSC1-5)2] (6–10), with their corresponding ligands 4-phenyl-1-(acetone)-thiosemicarbazone, HTSC1(1), 4-phenyl-1-(2′-chloro-benzaldehyde)-thiosemicarbazone, HTSC2(2), 4-phenyl-1-(3′-hydroxy-benzaldehyde)-thiosemicarbazone, HTSC3(3), 4-phenyl-1-(2′-naphthaldehyde)-thiosemicarbazone, HTSC4(4), and 4-phenyl-1-(1′-nitro-2′-naphthaldehyde)-thiosemicarbazone, HTSC5(5), were synthesized and characterized by elemental analysis and spectroscopic techniques (IR and1H- and13C-NMR). The molecular structure of HTSC3, HTSC4, and [Pd(TSC1)2] (6) have been determined by single crystal X-ray crystallography. Complex6shows a square planar geometry with two deprotonated ligands coordinated toPdIIthrough the azomethine nitrogen and thione sulfur atoms in acisarrangement. Thein vitrocytotoxic activity measurements indicate that the palladium(II) complexes (IC50=0.01–9.87 μM) exhibited higher antiproliferative activity than their free ligands (IC50=23.48–70.86 and >250 μM) against different types of human tumor cell lines. Among all the studied palladium(II) complexes, the [Pd(TSC3)2] (8) complex exhibited high antitumor activity on the DU145 prostate carcinoma and K562 chronic myelogenous leukemia cells, with low values of the inhibitory concentration (0.01 and 0.02 μM, resp.).Corrigendum to “Synthesis and Characterization of New Palladium(II) Thiosemicarbazone Complexes and Their Cytotoxic Activity against Various Human Tumor Cell Lines”


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