Characterization of cell line with dedifferentiated GIST‐like features established from cecal GIST of familial GIST model mice

Abstract

AbstractApproximately 40 families with multiple gastrointestinal stromal tumors (GISTs) and germline c‐kit gene mutations have been reported. Three knock‐in mouse models have been generated, and all the models showed a cecal GIST. In the present study, we established a cell line derived from cecal GIST in a familial GIST model mouse with KIT‐Asp818Tyr. Since the established cells showed spindle‐shaped morphology with atypical nuclei, and since immunohistochemistry revealed that they were positive for α‐SMA but negative for KIT, CD34 and desmin, the phenotypes of the cells were reminiscent of dedifferentiated GIST‐like ones but not the usual GIST‐like ones. Gene expression analysis showed that the cell line, designated as DeGISTL1 cell, did not express c‐kit gene apparently, but highly expressed HSP90 families and glutaminase 1. Pathway analysis of the cells revealed that metabolic pathway might promote their survival and growth. Pimitespib, a heat shock protein 90α/β inhibitor, and Telaglenastat, a selective glutaminase 1 inhibitor, inhibited proliferation of DeGISTL1 cells and the combination of these showed an additive effect. DeGISTL1 cells might be a good model of dedifferentiated GISTs, and combination of Pimitespib and Telaglenastat could be a possible candidate for treatment strategy for them.