Departmental Papers (Dental)

Document Type

Journal Article

Date of this Version

9-2017

Publication Source

Stem Cells

Volume

35

Issue

9

Start Page

2083

Last Page

2094

DOI

10.1002/stem.2666

Abstract

pithelial–mesenchymal transition (EMT), a biological process associated with cancer stem-like or cancer-initiating cell formation, contributes to the invasiveness, metastasis, drug resistance, and recurrence of the malignant tumors; it remains to be determined whether similar processes contribute to the pathogenesis and progression of ameloblastoma (AM), a benign but locally invasive odontogenic neoplasm. Here, we demonstrated that EMT- and stem cell-related genes were expressed in the epithelial islands of the most common histologic variant subtype, the follicular AM. Our results revealed elevated interleukin (IL)-6 signals that were differentially expressed in the stromal compartment of the follicular AM. To explore the stromal effect on tumor pathogenesis, we isolated and characterized both mesenchymal stromal cells (AM-MSCs) and epithelial cells (AM-EpiCs) from follicular AM and demonstrated that, in in vitro culture, AM-MSCs secreted a significantly higher level of IL-6 as compared to the counterpart AM-EpiCs. Furthermore, both in vitro and in vivo studies revealed that exogenous and AM-MSC-derived IL-6 induced the expression of EMT- and stem cell-related genes in AM-EpiCs, whereas such effects were significantly abrogated either by a specific inhibitor of STAT3 or ERK1/2, or by knockdown of Slug gene expression. These findings suggest that AM-MSC-derived IL-6 promotes tumor-stem like cell formation by inducing EMT process in AM-EpiCs through STAT3 and ERK1/2-mediated signaling pathways, implying a role in the etiology and progression of the benign but locally invasive neoplasm. Stem Cells 2017;35:2083–2094. © 2017 AlphaMed Press

Keywords

Ameloblastoma, Epithelial Cells, Epithelial–mesenchymal transition, Interleukin-6, Mesenchymal stromal cells, Tumor stem cells, Ameloblastoma, Animals, Carcinogenesis, Cell Separation, Epithelial Cells, Epithelial-Mesenchymal Transition, Female, Gene Expression Regulation, Neoplastic, Humans, Interleukin-6, Mesenchymal Stromal Cells, Mice, Nude, Signal Transduction, 2 (2 amino 3 methoxyphenyl)chromone, 2 morpholino 8 phenylchromone, 4 [[(4 methylphenyl)sulfonyloxy]acetamido]salicylic acid, interleukin 6, mitogen activated protein kinase 1, mitogen activated protein kinase 3, s 3i 201, STAT3 protein, transcription factor Slug, interleukin 6, ameloblastoma, animal experiment, animal tissue, Article, cancer patient, carcinogenesis, controlled study, epithelial mesenchymal transition, epithelium cell, female, follicular ameloblastoma, gene expression, human, in vitro study, in vivo study, mesenchymal stroma cell, mouse, nonhuman, signal transduction, ameloblastoma, animal, cell separation, epithelium cell, gene expression regulation, genetics, mesenchymal stroma cell, metabolism, nude mouse, pathology

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Date Posted: 10 February 2023

This document has been peer reviewed.