Polverini Peter J, Nör Felipe, Nör Jacques E
Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, United States.
Department of Cariology, Restorative Sciences, and Endodontics, University of Michigan School of Dentistry, Ann Arbor, MI, United States.
Front Oral Health. 2023 Jan 10;3:1095842. doi: 10.3389/froh.2022.1095842. eCollection 2022.
Cancer stem cells (CSC) are a subpopulation of cancer cells that exhibit properties of self-renewal and differentiation and have been implicated in metastasis and treatment failures. There is mounting evidence that carcinogen-initiated mucosal epithelial stem cells acquire the CSC phenotype following exposure to environmental or infectious mutagens and are responsible for promoting the malignant transformation of premalignant (dysplastic) epithelium. CSC further contribute to the progression of dysplasia by activating signaling pathways through crosstalk with various cell populations in the tumor microenvironment. Two cell types, tumor-associated macrophages (TAM) and vascular endothelial cells (EC) nurture CSC development, support CSC stemness, and contribute to tumor progression. Despite mounting evidence implicating CSC in the initiation and progression of dysplastic oral epithelium to squamous cell carcinoma (SCC), the molecular mechanisms underlying these synergistic biological processes remain unclear. This review will examine the mechanisms that underlie the transformation of normal epithelial stem cells into CSC and the mechanistic link between CSC, TAM, and EC in the growth and the malignant conversation of dysplastic oral epithelium.
癌症干细胞（CSC）是癌细胞的一个亚群，具有自我更新和分化的特性，并与转移和治疗失败有关。越来越多的证据表明，致癌物引发的黏膜上皮干细胞在接触环境或感染性诱变剂后会获得CSC表型，并导致癌前（发育异常）上皮细胞发生恶性转化。癌症干细胞通过与肿瘤微环境中的各种细胞群体相互作用激活信号通路，进一步促进发育异常的进展。两种细胞类型，即肿瘤相关巨噬细胞（TAM）和血管内皮细胞（EC），促进癌症干细胞的发育，维持癌症干细胞的干性，并促进肿瘤进展。尽管越来越多的证据表明癌症干细胞在发育异常的口腔上皮向鳞状细胞癌（SCC）的起始和进展过程中发挥作用，但这些协同生物学过程背后的分子机制仍不清楚。本综述将探讨正常上皮干细胞转化为癌症干细胞的机制，以及癌症干细胞、肿瘤相关巨噬细胞和血管内皮细胞在发育异常的口腔上皮生长和恶性转化中的机制联系。
