First in vitro study of human gastroenteropancreatic-neuroendocrine tumors: comparative effect of octreotide and pasireotide
A. Mohamed1, M. Blanchard1, M. Albertelli2, P. Niccoli3, G. Monges3, S. Garcia4, V. Moutardier4, J. Delpero3, A. Enjalbert1, T. Florio2, D. Ferone2, A. Saveanu1 & A. Barlier1
Somatostatin analogs (SSAs) such as octreotide (OCT) are currently effective in controlling most hypersecretion associated symptoms of Gastoenteropancreatic-neuroendocrinetumors (GEP-NETs). The results of the phase IIIb PROMID trial showed that OCT doubled time to progression for patients with metastatic neuroendocrine midgut tumors compared with placebo. SSAs act on different intracellular pathways through different somatostatin receptor (Sst) subtypes. While OCT is mainly an Sst2 agonist, Pasireotide (PAS) is a new universal ligand, binding to all Sst (except Sst4). Our aim was to compare on primary culture of human GEP-NETs the effect of OCT and PAS on cell viability, hormonal secretion and transduction pathways.
Methodology: This study was performed on 12 human GEP-NETs in vitro. The expression of SST subtypes mRNAs was evaluated and the trafficking of SST2 in presence of SSAs was followed by confocal microscopy.
Results: 1 Sst2 > Sst1 > Sst5 are expressed in all analysed GEP-NETs; 2/ Oct and PAS induced different Sst2 internalization patterns; 3/ OCT and PAS suppress cell viability at similar levels in all analysed tumors (range 2090%) through caspase dependant apoptosis process. 5/ Chromogranin A secretion is suppressed by both PAS and OCT in a dose dependant manner, close to the suppression observed in viability experiments. Conclusion: it is the first in vitro study on human GEP-NETs. PAS has a similar effect to OCT on cell viability and secretion of human GEP-NETs in vitro, despite a clear difference in Sst2 trafficking.
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This work was supported, however funding details are unavailable.