Division of Pathology, Department of Pathology and Microbiology, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan.
Department of Oral Surgery, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan.
Hum Cell. 2023 Mar;36(2):643-656. doi: 10.1007/s13577-023-00866-x. Epub 2023 Jan 30.
Squamous cell carcinoma (SCC) is the most major malignant tumor of the tongue. The tongue exists at the air-liquid interface and is covered with saliva. In addition, the tongue constituent cells and tongue cancer are present under fluid flow stimulation due to the abundant capillary network and contraction of muscle tissue. Therefore, replicating both cell-cell interactions (the cellular microenvironment) and the aforementioned physical microenvironment is very important for understanding the kinetics of tongue SCC. To elucidate the effects of the cellular and physical microenvironment on tongue SCC and to investigate the relationships between these factors, we developed a collagen cell disc, with double dish under a rotational culture method to generate cancer-stroma interactions and to create fluid flow stimulation. Mesenchymal cells, NIH-3T3 cells and tongue-derived fibroblasts influenced the proliferative potential. Extracellular signal-regulated kinase and p38 signaling were regulated either synergistically or independently by cellular interactions and fluid flow stimulation, depending on the SCC cell type. The cell-cell interactions and fluid flow stimulation independently, synergistically or contradictorily affected the behavior of tongue SCC. Fluid flow stimulation synergistically enhanced the antiproliferative effect of cis-diamminedichloroplatinum on tongue SCC cells, but mesenchymal cells abolished the synergistic antiproliferative effect related to fluid flow stimulation. In conclusion, a reconstructed model was established to investigate the cellular and physical microenvironments of tongue SCC in vitro. The newly established system is a promising model for the development of further regimes to treat general oral cancer.
鳞状细胞癌（SCC）是舌部最主要的恶性肿瘤。舌部位于气-液界面，被唾液覆盖。此外，由于丰富的毛细血管网络和肌肉组织的收缩，舌部细胞和舌部癌症会受到流体流动的刺激。因此，复制细胞-细胞相互作用（细胞微环境）和上述物理微环境对于了解舌鳞状细胞癌的动力学非常重要。为了阐明细胞和物理微环境对舌鳞状细胞癌的影响，并研究这些因素之间的关系，我们开发了一种胶原细胞盘，采用双盘旋转培养方法来产生癌-基质相互作用，并创建流体流动刺激。间充质细胞、NIH-3T3 细胞和舌源性成纤维细胞影响增殖潜力。细胞相互作用和流体流动刺激协同或独立调节细胞外信号调节激酶和 p38 信号通路，具体取决于 SCC 细胞类型。细胞-细胞相互作用和流体流动刺激独立、协同或矛盾地影响了舌鳞状细胞癌的行为。流体流动刺激协同增强了顺铂对舌鳞状细胞癌的抗增殖作用，而间充质细胞则消除了与流体流动刺激相关的协同抗增殖作用。总之，建立了一个体外研究舌鳞状细胞癌细胞和物理微环境的重建模型。新建立的系统是开发进一步治疗一般口腔癌的方案的有前途的模型。
