Telotristat ethyl affects crosstalk between tumor cells and stromal fibroblasts in small intestinal neuroendocrine tumors (SI-NETs)

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Introduction: SI-NETs are often associated with mesenteric fibrosis (MF) which causes significant morbidity and mortality. Telotristat ethyl (TE) was developed to treat carcinoid syndrome in SI-NET patients however, recent studies indicated TE could also have anti-tumor activity, the mechanism for which remains unclear.

Aim(s): This study aimed to investigate the potential effects of TE on SI-NET – fibroblast crosstalk in tumor progression and MF development.

Materials and methods: A co-culture paracrine in vitro model with GOT-1, a human midgut NET cell line, and LX2 a human fibroblast cell line was optimized. The optimal concentration of TE was assessed by MTS assay. Cell proliferation and serotonin secretion were quantified by BrdU ELISA and serotonin ELISA, respectively. Cells were treated with conditioned medium with/without TE for 72 hours followed by RNA sequencing and Gene Set Enrichment Analysis (GSEA). qRT-PCR and IHC was performed in tissue from 34 SI-NET patients grouped into 4 categories of mesenteric fibrosis severity.

Conference:

Presenting Author:

Authors: Hodgetts H, Martins M, Chen L, Laskaratos F, Hall A,

Keywords: fibrosis, fibroblast, crosstalk, telotristat, intestine, small, tumor,