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肿瘤干细胞(CSCs)对化疗和放射治疗耐药所致。本研究以水凝胶为生物材料，对头颈部肿瘤干细胞进行诱导培养。本研究旨在探讨水凝胶诱导HNCSCs的机制，建立HNCSCs的诊断方法，并建立临床应用的药物筛选体系。本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 Gels)，它能迅速将分化的癌细胞重新编程为CSCs。这项拟议的研究将首次利用这一原理来阐明水凝胶诱导癌细胞群体重编程的机制，以确定HNSCC的新的CSC标志物。我们2022财年的研究里程碑是阐明水凝胶诱导CSCs的机制。我们用四种HNSCC细胞(HSC2、HSC3、HSC4、Ca922)在DN凝胶上培养5天。实时荧光定量聚合酶链式反应检测肿瘤干细胞标志物(SOX-2、Nanog、Oct3/4、ALDH1)在1、3、5天的表达。随着时间的推移，所有癌症干细胞标记物的表达都会升高。从这些数据中，我们了解到，糖尿病肾病能迅速将分化的头颈部癌细胞重新编程为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.