Details

Autor(en) / Beteiligte

• Jiang, Chunmiao
• Zhang, Qunzhou
• Shanti, Rabie M.
• Shi, Shihong
• Chang, Ting‐Han
• Carrasco, Lee
• Alawi, Faizan
• Le, Anh D.

Titel

Mesenchymal Stromal Cell‐Derived Interleukin‐6 Promotes Epithelial–Mesenchymal Transition and Acquisition of Epithelial Stem‐Like Cell Properties in Ameloblastoma Epithelial Cells

Ist Teil von

• Stem cells (Dayton, Ohio), 2017-09, Vol.35 (9), p.2083-2094

Ort / Verlag

United States: Oxford University Press

Erscheinungsjahr

2017

Quelle

MEDLINE

Beschreibungen/Notizen

• Epithelial–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 IL‐6/IL‐6R‐mediated signaling pathways contribute to tumorigenesis and progression of ameloblastoma. Ameloblastoma‐derived mesenchymal stromal cells (AM‐MSCs) produce an abundant amount of interleukin‐6 (IL‐6), which activates the downstream ERK1/2 and STAT3 signaling pathways upon binding with its receptors (IL‐6R) on ameloblastoma epithelial cells (AM‐EpiCs). The activation of ERK1/2 and STAT3 signaling pathways subsequently promotes AM‐EpiCs to undergo epithelial‐mesenchymal transition (EMT) process and acquire epithelial stem‐like cell properties (AM‐EpiSCs). Within a tumor microenvironment enriched with IL‐6, both AM‐EpiCs and AM‐EpiSCs may continuously undergo EMT and a proportion of them may further transit into mesenchymal stromal‐like cells, thus contributing to the outgrowth and progression of this aggressive odontogenic benign tumor.