Stroma-oriented tumor microenvironment facilitates intraosseous ameloblastoma tumor growth [miRNA-Seq]

Here, we established an orthotopic intraosseous mouse model using ameloblastoma epithelial cells in combination with ameloblastoma-derived mesenchymal stromal cells (AMMSCs) or their secretome. AMMSC-derived extracellular vesicle-enriched secretome enhances stemness, epithelial-mesenchymal transition (EMT) phenotypes, and tumorigenic ability of ameloblastoma epithelial cells.

A unique signature of microRNAs in AMMSC-derived secretome is functionally associated with the upregulation of EMT-regulatory transcription factors in tumor epithelial cells. Single-nucleus ATAC and RNA sequencing revealed a dynamic EMT trajectory in primary human AM-derived epithelial cells activated by paired AMMSC-derived secretome. This study suggests that AMMSCs and their secretome drive orthotopic AM tumor development by promoting tumor epithelial cell proliferation, EMT, and vascular formation in the tumor microenvironment.