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

开发快速诱导头颈癌干细胞的方法以创新个性化治疗方式

• 批准号: 22K17010
• 负责人: ハビバ ウンマ
• 金额: $ 2.91万
• 依托单位: Hokkaido University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Early-Career Scientists
• 财政年份: 2022
• 资助国家: 日本
• 起止时间: 2022-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-22K17010/
• 关键词: cancer stem cells (CSCs); DN gels; drug-resistant; keyworad; cancer stem cells; head and neck cancer; hydrogel; reprogramming

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.

癌症复发可能是由于罕见的循环癌症干细胞（CSC）对化疗和放疗的耐药性。本研究的重点是使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，并建立临床应用的药物筛选体系。我们的实验室报道了由北海道大学（软湿物质实验室）开发的双网络水凝胶（DN凝胶），将分化的癌细胞快速重编程为CSC。该研究将首次利用该原理阐明水凝胶诱导癌细胞群重编程的机制，以识别HNSCC的新CSC标志物。我们2022财年的研究里程碑是阐明水凝胶诱导CSC的机制。我们用四种HNSCC细胞（HSC 2，HSC 3，HSC 4，Ca 922）在DN凝胶上培养五天，观察它们的形态学特征。通过实时PCR，我们以1天、3天和5天的间隔检查了癌症干细胞标志物（SOX-2、Nanog、OCt 3/4、ALDH 1）的表达。所有癌症干细胞标志物都显示其表达随时间推移而升高。从这些数据中，我们了解到DN凝胶快速将分化的头颈癌细胞重编程为HNCSC。