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

2022 Fiscal Year Research-status Report

• Project/Area Number: 22K17010
• Research Institution: Hokkaido University
• Principal Investigator: ハビバ ウンマ 北海道大学, 医学研究院, 客員研究員 (40755914)
• Project Period (FY): 2022-04-01 – 2025-03-31
• Keywords: cancer stem cells (CSCs) / DN gels / drug-resistant

Outline of Annual Research Achievements

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.

Current Status of Research Progress

3: Progress in research has been slightly delayed.

Reason

Currently, I can not do research as a full-time researcher. Due to my job responsibility, current research progress is slightly delayed. However, I could speed up my research from September 2023 onward.

Strategy for Future Research Activity

2023-2024 Fiscal Year Plan:
(I) To elucidate the mechanism of induction of CSCs by hydrogel by analysis of mechanosignal molecules and by genome/epigenome analysis
(II) To develop a CSC diagnostic method using hydrogel by Identifying new CSC markers (Microarray and RNAseq analysis will be performed) and creating a personalized medical hydrogel kit using Patient-derived primary cultured cells to determine hydrogel conditions that can predict human tumors' recurrence profile after treatment.
(III) To create seeds for CSC therapy using hydrogel by developing a drug screening system and identifying seeds using a hydrogel plate, we will do the drug screening, intending to obtain drug seeds that can be applied to medical treatment by performing large-scale screening targeting CSCs.

Causes of Carryover

I could not perform research as a full-time researcher due to my job responsibilities. However, I plan to speed up the investigation after taking a research leave from my institution. This is the reason for incurring the amount to be used to bear my research expenditure as proposed.