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Cellosaurus publication CLPUB00598
| Publication number | CLPUB00598 |
|---|---|
| Authors | Behrang Y. |
| Title | Establishment and characterization of a new human, highly differentiated and functionally active tumor model of a pancreatic neuroendocrine tumor. |
| Citation | Thesis MD (2020); University of Hamburg; Hamburg; Germany |
| Web pages | https://ediss.sub.uni-hamburg.de/handle/ediss/8633 |
| Abstract | The aim of this project was to characterize the newly established pancreatic NET cell line NT-3 and to study its behavior in direct comparison to the existing cell lines (QGP-1 and BON), upon treatment with therapeutics and as a xenograft animal model. This is to evaluate if NT-3 provides a representative, well-differentiated neuroendocrine tumor model for targeted and significant research on this tumor entity. Research on new therapies for pancreatic neuroendocrine tumors (pNET) has been hampered by the absence of a clinically relevant tumor model system. The neuroendocrine identity of NT-3 was verified by the expression of multiple NET-specific markers, which were highly expressed in NT-3 compared with BON and QGP-1. As a sign of functional activity, we were able to detect the expression and secretion of insulin in NT-3, corresponding to the clinical insulinoma of the patient providing the tumor that NT-3 was derived from. Until now, this well-differentiated phenotype is stable since 58 passages. The proliferative labeling index Ki-67 of 14.6% +- 1.0% in NT-3 is akin to the original tumor (15%-20%) and was lower than in BON (80.6% +- 3.3%) and QGP-1 (82.6% +- 1.0%). Moreover, NT-3 showed high expression of somatostatin receptors (SSTRs: 1, 2, 3, and 5), which are targets of therapeutics successfully used in the treatment of pancreatic NETs. In vivo growth was assessed in a xenograft mouse model. Upon subcutaneous transplantation of NT-3 cells, recipient mice developed tumors with an efficient tumor take rate (94%) and growth rate (139% +- 13%) by 4 weeks. Morphology and neuroendocrine marker expression of xenograft tumors resembled the original human tumor. These outstanding characteristics qualify NT-3 as a relevant model to study neuroendocrine tumor biology and to develop new NET treatments. |
| Cell lines | CVCL_3985; BON-1 CVCL_VG81; NT-3 CVCL_3143; QGP-1 |