Goto Yuriko, Ibi Miho, Sato Hirotaka, Tanaka Junichi, Yasuhara Rika, Aota Keiko, Azuma Masayuki, Fukada Toshiyuki, Mishima Kenji, Irié Tarou
Division of Anatomical and Cellular Pathology, Department of Pathology, Iwate Medical University, 1-1-1 Idaidori, Yahaba-cho, Shiwa-gun, Iwate, 028-3694, Japan.
Division of Pathology, Department of Oral Diagnostic Sciences, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan.
J Oral Biosci. 2020 Mar;62(1):99-106. doi: 10.1016/j.job.2020.01.002. Epub 2020 Jan 30.
Details of the histogenesis of salivary gland tumors are largely unknown. The oncogenic role of PLAG1 in the salivary gland has been demonstrated in vivo. Herein, we demonstrate PLAG1 roles in the acinar and ductal cells of normal human salivary glands to clarify the early events that occur during the histogenesis of salivary gland tumors.
Normal salivary gland cells with acinar and ductal phenotypes were transfected with PLAG1 plasmid DNA. Subsequently, PLAG1 overexpressed and mock cells were examined by cell proliferation, transwell migration, and salisphere formation assays. Differentiation and salivary and pluripotent stem cell marker expression levels were evaluated by quantitative reverse transcription-polymerase chain reaction and immunofluorescence. Alterations in transcriptional expressions were investigated via cap analysis of gene expression with gene-enrichment and functional annotation analysis.
PLAG1 promoted cell proliferation and transwell migration in the acinar and ductal cells, and markedly enhanced the stemness profiles and luminal cell-like profiles in acinar cells; the stemness profiles were partially increased in the ductal cells.
PLAG1 enhanced the stemness profiles in the acinar cells of normal human salivary glands in a cell type-specific manner. Thus, it may be involved in salivary gland tumorigenesis by increasing the stemness character of the normal salivary gland cells.
唾液腺肿瘤的组织发生细节大多未知。PLAG1在唾液腺中的致癌作用已在体内得到证实。在此，我们证明PLAG1在正常人类唾液腺的腺泡细胞和导管细胞中的作用，以阐明唾液腺肿瘤组织发生过程中早期发生的事件。
用PLAG1质粒DNA转染具有腺泡和导管表型的正常唾液腺细胞。随后，通过细胞增殖、Transwell迁移和唾液球形成试验检测PLAG1过表达细胞和对照细胞。通过定量逆转录-聚合酶链反应和免疫荧光评估分化以及唾液和多能干细胞标志物的表达水平。通过基因表达的帽分析以及基因富集和功能注释分析研究转录表达的变化。
PLAG1促进腺泡细胞和导管细胞的细胞增殖和Transwell迁移，并显著增强腺泡细胞的干性特征和管腔样细胞特征；导管细胞的干性特征部分增加。
PLAG1以细胞类型特异性方式增强正常人类唾液腺腺泡细胞的干性特征。因此，它可能通过增加正常唾液腺细胞的干性特征而参与唾液腺肿瘤发生。
