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Updated: Oct 13, 2025
Modeling Oral-Esophageal Squamous Cell Carcinoma in 3D Organoids
Published on: December 23, 2022
Characterization of normal and cancer stem-like cell populations in murine lingual epithelial organoids using
Erik Johansson1,2, Hiroo Ueno3,4
1Department of Stem Cell Pathology, Kansai Medical University, 2-5-1 Shin-machi, Hirakata, Osaka, 573-1010, Japan.
Abstract:
The advances in oral cancer research and therapies have not improved the prognosis of patients with tongue cancer. The poor treatment response of tongue cancer may be attributed to the presence of heterogeneous tumor cells exhibiting stem cell characteristics. Therefore, there is a need to develop effective molecular-targeted therapies based on the specific gene expression profiles of these cancer stem-like cell populations. In this study, the characteristics of normal and cancerous organoids, which are convenient tools for screening anti-cancer drugs, were analyzed comparatively. As organoids are generally generated by single progenitors, they enable the exclusion of normal cell contamination from the analyses. Single-cell RNA sequencing analysis revealed that p53 signaling activation and negative regulation of cell cycle were enriched characteristics in normal stem-like cells whereas hypoxia-related pathways, such as HIF-1 signaling and glycolysis, were upregulated in cancer stem-like cells. The findings of this study improved our understanding of the common features of heterogeneous cell populations with stem cell properties in tongue cancers, that are different from those of normal stem cell populations; this will enable the development of novel molecular-targeted therapies for tongue cancer.
Insights
Tongue cancer stem-like cells show distinct molecular features compared to normal cells. Understanding these differences, like upregulated hypoxia pathways in cancer cells, is key for developing targeted therapies.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Stem Cell Research
Background:
- Despite advances, tongue cancer prognosis remains poor, potentially due to heterogeneous cancer stem-like cells.
- Effective molecular-targeted therapies require understanding the unique gene expression profiles of these cells.
Purpose of the Study:
- To comparatively analyze normal and cancerous organoids to identify distinct characteristics of tongue cancer stem-like cells.
- To provide a basis for developing novel molecular-targeted therapies for tongue cancer.
Main Methods:
- Organoid generation and comparative analysis of normal and cancerous models.
- Single-cell RNA sequencing to profile gene expression in stem-like cell populations.
Main Results:
- Normal stem-like cells showed enriched p53 signaling and cell cycle regulation.
- Cancer stem-like cells exhibited upregulated hypoxia-related pathways, including HIF-1 signaling and glycolysis.
Conclusions:
- Identified key molecular differences between normal and tongue cancer stem-like cells.
- Findings pave the way for developing targeted therapies by exploiting unique cancer stem-like cell vulnerabilities.
