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

Autor: Sano D; Department of Surgical Pathology, Hyogo Medical University School of Medicine, Nishinomiya, Japan., Kihara T; Department of Surgical Pathology, Hyogo Medical University School of Medicine, Nishinomiya, Japan., Yuan J; Department of Pathology, The First People's Hospital of Foshan, Foshan, Republic of China., Kimura N; Department of Surgical Pathology, Hyogo Medical University School of Medicine, Nishinomiya, Japan., Ohkouchi M; Department of Surgical Pathology, Hyogo Medical University School of Medicine, Nishinomiya, Japan., Hashikura Y; Department of Surgical Pathology, Hyogo Medical University School of Medicine, Nishinomiya, Japan., Ohkubo S; Discovery and Preclinical Research Division, Taiho Pharmaceutical Co. Ltd, Tsukuba, Japan., Hirota S; Department of Surgical Pathology, Hyogo Medical University School of Medicine, Nishinomiya, Japan.
Jazyk: angličtina
Zdroj: Pathology international [Pathol Int] 2023 May; Vol. 73 (5), pp. 181-187. Date of Electronic Publication: 2023 Feb 24.
DOI: 10.1111/pin.13315
Abstrakt: Approximately 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.
(© 2023 The Authors. Pathology International published by Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.)
Databáze: MEDLINE
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