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Updated: Aug 8, 2026
Modeling Oral-Esophageal Squamous Cell Carcinoma in 3D Organoids
Published on: December 23, 2022
Relationship between peroxisome proliferator-activated receptor-gamma expression and differentiation of human
Takashi Takashima1, Yasuhiro Fujiwara, Masaki Hamaguchi
1Department of Gastroenterology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan. d98m011@ med.osaka-cu.ac.jp
Abstract:
Peroxisome proliferator-activated receptor-gamma (PPAR-gamma), a member of the nuclear hormone receptor superfamily, is involved in suppressing the growth of several tumors. We showed that PPAR-gamma is expressed in Barrett's adenocarcinoma cell lines and inhibited the growth of these lines through the induction of G1 cell cycle arrest and apoptosis. We examined PPAR-gamma expression in human esophageal squamous cell carcinoma (SCC) in vitro and in vivo and investigated whether PPAR-gamma ligands affect the proliferation and apoptosis of human SCC cell lines. Biopsy specimens (n=46) obtained from human SCC of the esophagus were stained using a monoclonal antibody against human PPAR-gamma. We assessed the effects of PPAR-gamma ligands on the growth of SCC cells by adding 15-deoxy prostaglandin J2 (15d-PGJ2), or troglitazone to six human esophageal SCC cell lines (TE-1, TE-2, TE-3, TE-5, TE-8, and TE-9). Immunohistochemical staining showed that 34 of 46 (73.9%) SCC of the esophagus expressed PPAR-gamma. All SCC cell lines expressed PPAR-gamma mRNA and protein, especially when poorly differentiated (TE-2, TE-5, and TE-9). The PPAR-gamma ligands significantly and dose-dependently inhibited the proliferation of SCC lines, except for well-differentiated TE-1 and TE-3. Apoptosis was induced by 15d-PGJ2 (10 microM) in all tested SCC lines except TE-1, whereas troglitazone (50 microM) was marginally effective in only the TE-2 and TE-3 cell lines. The present findings suggest that PPAR-gamma could be a therapeutic target for treating squamous cell carcinoma of the esophagus, possibly through the induction of apoptosis.
Insights
Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) shows promise as a therapeutic target for esophageal squamous cell carcinoma (SCC). Its ligands inhibit SCC cell proliferation and induce apoptosis, suggesting a new treatment avenue.
Area of Science:
- Molecular Biology
- Oncology
- Cell Biology
Background:
- Peroxisome proliferator-activated receptor-gamma (PPAR-gamma), a nuclear hormone receptor, is implicated in tumor growth suppression.
- Previous studies demonstrated PPAR-gamma's inhibitory effects on Barrett's adenocarcinoma cell lines via cell cycle arrest and apoptosis.
- The role of PPAR-gamma in esophageal squamous cell carcinoma (SCC) and the efficacy of its ligands remain to be fully elucidated.
Purpose of the Study:
- To investigate PPAR-gamma expression in human esophageal squamous cell carcinoma (SCC) in vitro and in vivo.
- To determine the effects of PPAR-gamma ligands on the proliferation and apoptosis of human SCC cell lines.
Main Methods:
- Immunohistochemical staining of 46 human esophageal SCC biopsy specimens for PPAR-gamma expression.
- Assessment of PPAR-gamma mRNA and protein in six human esophageal SCC cell lines (TE-1, TE-2, TE-3, TE-5, TE-8, TE-9).
- Treatment of SCC cell lines with PPAR-gamma ligands (15-deoxy prostaglandin J2 [15d-PGJ2] and troglitazone) to evaluate proliferation and apoptosis.
Main Results:
- PPAR-gamma expression was detected in 73.9% (34/46) of esophageal SCC biopsy specimens.
- All tested SCC cell lines expressed PPAR-gamma, with higher levels in poorly differentiated lines.
- PPAR-gamma ligands significantly inhibited SCC cell proliferation dose-dependently (except in well-differentiated lines) and induced apoptosis (15d-PGJ2 was more effective than troglitazone).
Conclusions:
- PPAR-gamma is expressed in human esophageal squamous cell carcinoma.
- PPAR-gamma ligands demonstrate anti-proliferative and pro-apoptotic effects on esophageal SCC cells.
- PPAR-gamma represents a potential therapeutic target for esophageal squamous cell carcinoma treatment.
