Crosstalk between cancer-associated fibroblasts and small intestinal neuroendocrine tumour cells in a 3D spheroid model

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Introduction: At diagnosis, over 50% of small intestinal neuroendocrine tumours (SI-NETs) have metastasised to the mesentery where they often induce extensive fibrosis. Recent studies highlight the crucial interaction between SI-NET cells and cancer-associated fibroblasts (CAFs) in the pathogenesis of mesenteric fibrosis (MF).

Aim(s): Our aim is to study this interaction in a newly developed 3D spheroid model representing the tumour microenvironment.

Materials and methods: CAFs from SI-NET tissue (primary tumour, mesenteric metastasis, or adjacent mesentery) were isolated, cultured, and characterised using immunohistochemical stainings and RT-qPCR. Mono- and co-cultured spheroids were generated with patient-derived CAFs and GOT1 cells, a SI-NET metastasis-derived cell line. The spheroids were immunohistochemically characterised for proliferation (Ki-67), activation (αSMA, COL1A1), and identification (vimentin). Cell number of the spheroids was quantified using flow cytometry.

Conference:

Presenting Author:

Authors: van der Slik E, Feelders R, van Koetsveld P, Iyer A, Hofland J,

Keywords: mesenteric fibrosis, small intestinal neuroendocrine tumour, CAF,