Department of Otolaryngology, Leroy T. Canoles Jr. Cancer Research Center, Eastern Virginia Medical School, Norfolk, VA, United States.
School of Medical Diagnostic and Translational Sciences, College of Health Sciences, Old Dominion University, Norfolk, VA, United States.
Pathology. 2018 Aug;50(5):524-529. doi: 10.1016/j.pathol.2018.03.002. Epub 2018 Jun 8.
Interest into the cellular biology of human tonsillar crypts has grown in recent years because it is now known to be the site of origin of most human papilloma virus (HPV) induced oropharyngeal squamous cell carcinomas (OPSCC). Despite the interest, still relatively little is known regarding the cellular hierarchy and dynamics of this anatomical subsite. Here we evaluate normal tonsillar crypts for expression of putative stem cell markers. We found that ALDH1A1 was uniquely expressed in a subset of suprabasal tonsillar crypt epithelium. This cell population was unique from NGFR expressing cells, which were previously identified to have stem/progenitor activity in vitro. In vivo mitochondrial lineage tracing was consistent with a basal to luminal progression of cellular development. This provides support for NGFR cells as the resident stem/progenitor cells in tonsillar crypts, and suggests that the ALDH1A1 cells are not stem/progenitor cells, but merely a unique component of the crypt cellular microenvironment. Analysis of tumours found that both NGFR and ALDH1A1 are lost in HPV+ and HPV- tumours, while LGR5 expression is induced in the same tumours. These results identify a unique component of the tonsillar crypt epithelium-ALDH1A1 cells-and support a cellular model where NGFR+ cells are the long-lived progenitor cells within tonsillar crypts. They also provide evidence that NGFR and ALDH1A1+ cells are lost during tumourigenesis.
近年来，人们对人类扁桃体隐窝的细胞生物学产生了浓厚的兴趣，因为现在已知它是大多数人乳头瘤病毒（HPV）诱导的口咽鳞状细胞癌（OPSCC）的起源部位。尽管人们对此很感兴趣，但对于这个解剖亚部位的细胞层次结构和动态仍然知之甚少。在这里，我们评估了正常扁桃体隐窝中潜在干细胞标志物的表达情况。我们发现，ALDH1A1 仅在扁桃体隐窝上皮的一部分基底上层中表达。这个细胞群体与之前在体外被鉴定具有干细胞/祖细胞活性的 NGFR 表达细胞不同。体内线粒体谱系追踪与细胞发育从基底到腔的进展一致。这为 NGFR 细胞作为扁桃体隐窝中的常驻干细胞/祖细胞提供了支持，并表明 ALDH1A1 细胞不是干细胞/祖细胞，而仅仅是隐窝细胞微环境的一个独特组成部分。对肿瘤的分析发现，HPV+ 和 HPV- 肿瘤中均丢失了 NGFR 和 ALDH1A1，而 LGR5 表达在相同的肿瘤中被诱导。这些结果确定了扁桃体隐窝上皮的一个独特组成部分——ALDH1A1 细胞，并支持一种细胞模型，即 NGFR+ 细胞是扁桃体隐窝中的长寿祖细胞。它们还提供了证据表明，在肿瘤发生过程中，NGFR 和 ALDH1A1+ 细胞丢失。
