3D Primary Cell Culture: A Novel Preclinical Model For Pancreatic Neuroendocrine Tumors (PanNETs)

April-Monn, Simon Leonhard; Wiedmer, Tabea; Skowronska, Magdalena; Maire, Renaud; Schiavo Lena, Marco; Trippel, Mafalda; Di Domenico, Annunziata; Muffatti, Francesca; Andreasi, Valentina; Capurso, Gabriele; Doglioni, Claudio; Kim-Fuchs, Corina; Gloor, Beat; Zatelli, Maria Chiara; Partelli, Stefano; Falconi, Massimo; Perren, Aurel; Marinoni, Ilaria (2020). 3D Primary Cell Culture: A Novel Preclinical Model For Pancreatic Neuroendocrine Tumors (PanNETs) (In Press). Neuroendocrinology Karger 10.1159/000507669

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Molecular mechanisms underlying the development and progression of PanNET are still insufficiently understood. Efficacy of currently approved PanNET therapies is limited. While novel treatment options are being developed, patient stratification permitting more personalized treatment selection in PanNET is yet not feasible since no predictive markers are established. The lack of representative in vitro and in vivo models as well as the rarity and heterogeneity of PanNET are prevailing reasons for this. In this study, we describe an in vitro 3D human primary PanNET culture system as a novel preclinical model for more personalized therapy selection. We present a screening platform allowing multi-center sample collection and drug screening in 3D cultures of human primary PanNET cells. We demonstrate that primary cells isolated from PanNET patients and cultured in vitro form islet-like tumoroids. Islet-like tumoroids retain the neuroendocrine phenotype and are viable for at least two weeks in culture with high success rate (86%). Viability can be monitored continuously allowing for a per-well normalization. In a proof-of-concept study, islet-like tumoroids were screened with three clinically approved therapies for PanNET: Sunitinib, everolimus and temozolomide. Islet-like tumoroids display varying in vitro response profiles to distinct therapeutic regimes. Treatment response of islet-like tumoroids (IC50) differs also between patient samples. We believe that the presented human PanNET screening platform is suitable for personalized drug testing in a larger patient cohort and a broader application will help in identifying novel markers predicting treatment response and in refining PanNET therapy.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology
04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Visceral Surgery
04 Faculty of Medicine > Service Sector > Institute of Pathology > Translational Research Unit

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

April-Monn, Simon; Skowronska, Magdalena; Maire, Renaud Sylvain; Trippel, Mafalda Arasceli; Di Domenico, Annunziata; Kim-Fuchs, Corina; Gloor, Beat; Perren, Aurel and Marinoni, Ilaria

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

0028-3835

Publisher:

Karger

Language:

English

Submitter:

Simon April-Monn

Date Deposited:

28 Apr 2020 10:41

Last Modified:

28 Jul 2020 15:31

Publisher DOI:

10.1159/000507669

PubMed ID:

32241015

Uncontrolled Keywords:

Pancreatic neuroendocrine tumor, PanNET, NET, 3D culture, preclinical model, primary cells, drug screening, islet-like tumoroids, spheroids, organoids

BORIS DOI:

10.7892/boris.143343

URI:

https://boris.unibe.ch/id/eprint/143343

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