Development of a method for rapid induction of head and neck cancer stem cells for innovation of personalized therapeutic modality

癌症复发可能是由于罕见的循环癌症干细胞（CSCs）对化疗和放疗产生耐药性。本研究的重点是利用水凝胶作为生物材料诱导头颈癌干细胞（HNCSCs）。本研究旨在探讨水凝胶诱导HNCSCs的机制，建立HNCSCs的诊断方法，建立临床应用的药物筛选系统。我们的实验室报道了一种由北海道大学（软湿物质实验室）开发的双网络水凝胶（DN凝胶），可以快速将分化的癌细胞重编程为csc。该研究将首次利用这一原理阐明水凝胶诱导癌细胞群重编程的机制，以鉴定HNSCC的新CSC标记物。我们2022财年的研究里程碑是阐明水凝胶诱导CSCs的机制。我们对水凝胶诱导的球形头颈部鳞状癌细胞进行了表征。我们选用4个HNSCC细胞（HSC2、HSC3、HSC4、Ca922），在DN凝胶上培养5天。通过Real-time PCR，我们每隔1天、3天和5天检测肿瘤干细胞标志物（SOX-2、Nanog、OCt3/4、ALDH1）的表达。随着时间的推移，所有癌症干细胞标记物的表达都有所升高。从这些数据中，我们了解到DN凝胶可以迅速将分化的头颈部癌细胞重编程为HNCSCs。

Cancer recurrence can arise due to rare circulating cancer stem cells (CSCs) resistant to chemotherapies and radiotherapies. This research focuses on the induction of head and neck cancer stem cells (HNCSCs) using hydrogel as a biomaterial. The study aims to Investigate the mechanism of HNCSCs induction by the hydrogel, to develop a diagnostic method for HNCSCs, and to establish a drug screening system for clinical application. Our laboratory reported that a double-network hydrogel (DN gels), developed by Hokkaido University (Laboratory of Soft and Wet Matter), rapidly reprogrammed differentiated cancer cells into CSCs. The proposed study will be the first to use this principle to elucidate the mechanism of hydrogel-induced reprogramming of cancer cell populations to identify new CSC markers of HNSCC.Our research milestone for the fiscal year 2022 was to Elucidate the mechanism of induction of CSCs by the hydrogel. We characterized the hydrogel-induced sphere forming Head neck squamous carcinoma cells.We used four HNSCC cells (HSC2, HSC3, HSC4, Ca922) and cultured them on DN gels for five days. By Real-time PCR, we checked cancer stem cell markers (SOX-2, Nanog, OCt3/4, ALDH1) expression at 1-, 3-, and 5-day intervals. All cancer stem cell markers show their elevated expression as time elapses. From this data, we understand that DN gels rapidly reprogrammed differentiated Head and neck cancer cells into HNCSCs.