PLAG1 overexpression in salivary gland duct-acinar units results in epithelial tumors with acinar-like features: Tumorization of luminal stem/progenitor cells may result in the development of salivary gland tumors consisting of only luminal cells

Abstract

Objectives

Details about salivary gland tumor histogenesis remain unknown. Here, we established a newly generated murine salivary gland tumor model that could overexpress pleomorphic adenoma gene 1 (PLAG1) and attempted to clarify the events that occur during the early phase of salivary gland tumor histogenesis.

Methods

Salivary gland tumors were generated using murine models (Sox9IRES-CreERT2; ROSA26-PLAG1). Lineage tracing of Sox9-expressing cells was performed using Sox9IRES-CreERT2; ROSA26-tdTomato mice, which were generated by crossing Sox9^CreERT2/- and ROSA26-tdTomato mice (expressing the tdTomato fluorescent protein). Organ-cultured embryonic salivary glands from the murine model were morphologically analyzed, and mRNA sequencing was conducted two days after tumor induction for gene enrichment and functional annotation analysis.

Results

Salivary gland tumors exhibited epithelial features with acinar-like structures because of gene rearrangements in the luminal cells. Structural disturbances in the duct-acinar unit of the salivary gland were observed and cancer-related pathways were enriched among the differentially upregulated genes in the early phase of tumor induction in an organ-cultured embryonic salivary gland tumor model.

Conclusions

The newly generated murine salivary gland tumor model may show that the tumorization of luminal stem/progenitor cells can result in the development of salivary gland tumors comprising only luminal cells.