Hanashima Katsuyuki, Akutagawa Takashi, Yamamoto-Rikitake Mihoko, Sakumoto Takehisa, Futamata Maki, Nakao Yoshifumi, Yokoyama Masatoshi, Toda Shuji, Aoki Shigehisa
Department of Pathology and Microbiology, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga, Saga 849-8501, Japan.
Department of Obstetrics and Gynecology, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga, Saga 849-8501, Japan.
Acta Histochem Cytochem. 2021 Oct 29;54(5):155-165. doi: 10.1267/ahc.21-00038. Epub 2021 Oct 6.
The mechanisms controlling the aggressiveness and survival of cervical SCC cells remain unclear. We investigated how the physical and biological microenvironments regulate the growth, apoptosis and invasiveness of cervical cancer cells. Dynamic flow and air exposure were evaluated as physical microenvironmental factors, and stromal fibroblasts were evaluated as a biological microenvironmental factor. To investigate any regulatory effects of these microenvironmental factors, we established a new culture model which concurrently replicates fluid streaming, air exposure and cancer-stromal interactions. Three cervical cancer cell lines were cultured with or without NIH 3T3 fibroblasts. Air exposure was realized using a double-dish culture system. Dynamic flow was created using a rotary shaker. Dynamic flow and air exposure promoted the proliferative activity and decreased the apoptosis of cervical cancer cells. Fibroblasts regulated the invasive ability, growth and apoptosis of cervical cancer cells. Extracellular signal-regulated kinase and p38 signaling were regulated either synergistically or independently by dynamic flow, air exposure and cellular interactions, depending on the cervical cancer cell type. This study demonstrates that the physical and biological microenvironments interact to regulate the aggressiveness and survival of cervical cancer cells. Our simple culture system is a promising model for developing further treatment strategies for various types of cancer.
控制宫颈鳞状细胞癌（SCC）细胞侵袭性和生存的机制仍不清楚。我们研究了物理和生物微环境如何调节宫颈癌细胞的生长、凋亡和侵袭性。将动态流动和空气暴露评估为物理微环境因素，将基质成纤维细胞评估为生物微环境因素。为了研究这些微环境因素的任何调节作用，我们建立了一种新的培养模型，该模型同时复制流体流动、空气暴露和癌-基质相互作用。在有或没有NIH 3T3成纤维细胞的情况下培养三种宫颈癌细胞系。使用双培养皿系统实现空气暴露。使用旋转振荡器产生动态流动。动态流动和空气暴露促进了宫颈癌细胞的增殖活性并减少了其凋亡。成纤维细胞调节宫颈癌细胞的侵袭能力、生长和凋亡。细胞外信号调节激酶和p38信号通路受动态流动、空气暴露和细胞相互作用协同或独立调节，这取决于宫颈癌细胞类型。本研究表明，物理和生物微环境相互作用以调节宫颈癌细胞的侵袭性和生存。我们的简单培养系统是开发针对各种类型癌症的进一步治疗策略的有前景的模型。
