1 Department of Oral and Maxillofacial Surgery, The Affiliated Hospital of Qingdao University, Shandong, China.
4 School of Stomatology, Qingdao University, Shandong, China.
J Dent Res. 2018 Jun;97(6):654-664. doi: 10.1177/0022034518756351. Epub 2018 Feb 27.
Head and neck cancer is one of the most frequent human malignancies worldwide, with a high rate of recurrence and metastasis. Head and neck squamous cell carcinoma (HNSCC) is cellularly and molecularly heterogeneous, with subsets of undifferentiated cancer cells exhibiting stem cell-like properties, called cancer stem cells (CSCs). Epithelial-mesenchymal transition, gene mutation, and epigenetic modification are associated with the formation of cellular plasticity of tumor cells in HNSCC, contributing to the acquisition of invasive, recurrent, and metastatic properties and therapeutic resistance. Tumor microenvironment (TME) plays a supportive role in the initiation, progression, and metastasis of head and neck cancer. Stromal fibroblasts, vasculature, immune cells, cytokines, and hypoxia constitute the main components of TME in HNSCC, which contributes not only to the acquisition of CSC properties but also to the recurrence and therapeutic resistance of the malignancies. In this review, we discuss the potential mechanisms underlying the development of cellular plasticity, especially the emergence of CSCs, in HNSCC. We also highlight recent studies implicating the complex interplays among TME components, plastic CSCs, tumorigenesis, recurrence, and therapeutic resistance of HNSCC. Finally, we summarize the treatment modalities of HNSCC and reinforce the novel concept of therapeutic targeting CSCs in HNSCC.
头颈部癌症是全球最常见的人类恶性肿瘤之一，具有很高的复发和转移率。头颈部鳞状细胞癌（HNSCC）在细胞和分子上具有异质性，其中一些未分化的癌细胞具有干细胞样特性，称为癌症干细胞（CSCs）。上皮-间充质转化、基因突变和表观遗传修饰与 HNSCC 中肿瘤细胞的细胞可塑性形成有关，导致侵袭性、复发性和转移性以及治疗耐药性的获得。肿瘤微环境（TME）对头颈部癌症的发生、发展和转移起着支持作用。间质成纤维细胞、血管、免疫细胞、细胞因子和缺氧构成了 HNSCC 中 TME 的主要成分，不仅有助于获得 CSC 特性，还导致恶性肿瘤的复发和治疗耐药性。在这篇综述中，我们讨论了 HNSCC 中细胞可塑性发展的潜在机制，特别是 CSCs 的出现。我们还强调了最近的研究表明 TME 成分、可塑性 CSCs、肿瘤发生、复发和 HNSCC 治疗耐药性之间的复杂相互作用。最后，我们总结了 HNSCC 的治疗方式，并强调了治疗靶向 HNSCC 中 CSCs 的新观念。
