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Endocrine Abstracts (2022) 81 RC6.2 | DOI: 10.1530/endoabs.81.RC6.2

ECE2022 Rapid Communications Rapid Communications 6: Endocrine-Related Cancer (8 abstracts)

Reciprocal interactions between fibroblast and pancreatic neuroendocrine tumor cells: putative impact of the tumor microenvironment

Thomas Cuny 1 , Gregoire Mondielli 1 , Peter van Koetsveld 2 , Wouter de Herder 2 , Anne Barlier 1 & Leo Hofland 2


1Aix Marseille University, INSERM, U1251, Marseille Medical Genetics, Marseille, France; 2Division Endocrinology, Erasmus Medical Center, Department of Internal Medicine, Rotterdam, Netherlands


Introduction: Pancreatic neuroendocrine neoplasms (PNEN) present with a fibrotic stroma which constitutes the tumor microenvironment (TME). The role played by stromal fibroblasts over the growth of PNEN and their sensitivity to the mTOR inhibitor, RAD001, are as yet unestablished.

Methods: We investigated reciprocal interactions between 1) human PNEN cell lines (BON-1/QGP-1) or primary cultures of human ileal neuroendocrine neoplasm (iNEN) or PNEN, and 2) human fibroblast cell lines (HPF/HFL-1). Proliferation was assessed in transwell co-culture (HFL-1tw, HPFtw, BON-1tw, QGPtw) or in the presence of serum-free conditioned media (BON-1cm, QGP-1cm, HFL-1cm, HPFcm), with and without RAD001. Migration of BON-1/QGP-1 was evaluated when incubated with HPFcm.

Results: Proliferation of BON-1 and QGP-1 increased in the presence of HFL-1cm, HPFcm, HFL-1tw and HPFtw (BON-1: +46 to +70% and QGP-1: +42 to +55% P< 0.001 vs controls for both), whereas this stimulatory effect was reversed in presence of RAD001. Likewise, proliferation of human iNEN and PNEN primary cultures increased in presence of HFL-1 or HPF. Reciprocally, BON-1cm and BONtw stimulated the proliferation of HPF (+90 +/- 61% and +55 +/- 47% respectively, P< 0.001 vs controls), an effect less pronounced with either QGP-1cm or QGPtw (+19 to + 27%, P< 0.05 vs controls) and unmodified by RAD001. RAD001 resulted in a decrease of colony number of BON-1 and QGP-1, while colony size remained the same in presence of the drug. Finally, a higher migration potential of BON-1 and QGP-1 occurred in presence of HPFcm (P< 0.001 vs basal).

Conclusions: Fibroblasts, in the TME of PNEN, represent a target of interest to control escape from mTOR inhibitors tumor growth and dissemination.

Volume 81

European Congress of Endocrinology 2022

Milan, Italy
21 May 2022 - 24 May 2022

European Society of Endocrinology 

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