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Updated: Jul 4, 2025
03:36
Development of Compendium for Esophageal Squamous Cell Carcinoma
Published on: April 12, 2024
422
Periostin in Cancer-Associated Fibroblasts Promotes Esophageal Squamous Cell Carcinoma Progression by Enhancing
Shoji Miyako1, Yu-Ichiro Koma2, Takashi Nakanishi1
1Division of Pathology, Department of Pathology, Kobe University Graduate School of Medicine, Kobe, Japan; Division of Gastro-intestinal Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.
The American Journal of Pathology
|February 6, 2024
Summary
Cancer-associated fibroblasts (CAFs) promote esophageal cancer progression. Targeting periostin (POSTN), a protein highly expressed by CAFs, may offer a new therapeutic strategy for esophageal squamous cell carcinoma (ESCC).
Area of Science:
- Oncology
- Cancer Biology
- Tumor Microenvironment Research
Background:
- Cancer-associated fibroblasts (CAFs) are key players in the tumor microenvironment, driving the progression of various cancers, including esophageal squamous cell carcinoma (ESCC).
- Understanding the specific contributions of CAFs and their secreted factors is crucial for developing effective cancer therapies.
Purpose of the Study:
- To investigate the role of periostin (POSTN), a protein highly expressed by CAF-like cells, in the progression of esophageal squamous cell carcinoma (ESCC).
- To explore POSTN as a potential therapeutic target for ESCC.
Main Methods:
- Generated CAF-like cells by co-culturing human bone marrow-derived mesenchymal stem cells with ESCC cells.
- Assessed the impact of POSTN on ESCC cell phenotypes, Akt and Erk signaling pathways, and migration using recombinant POSTN and siRNA-mediated POSTN suppression.
- Investigated the role of the POSTN receptor, integrin β4, in ESCC cells.
- Analyzed POSTN expression in patient tumor tissues and correlated it with clinical outcomes and tumor characteristics.
Main Results:
- CAF-like cells highly expressed POSTN, and co-culture with ESCC cells enhanced ESCC survival, growth, and migration via Akt and Erk activation.
- Recombinant POSTN mimicked these effects, while POSTN suppression in CAF-like cells abrogated the enhanced ESCC phenotypes.
- POSTN also promoted migration of mesenchymal stem cells and macrophages, inducing tumor-associated macrophage-like properties.
- High stromal POSTN expression in ESCC patients correlated significantly with advanced tumor invasion, vascular invasion, higher pathologic stage, and poor outcomes.
Conclusions:
- CAF-secreted POSTN plays a significant role in shaping the tumor microenvironment and promoting ESCC progression.
- POSTN signaling, mediated by integrin β4, activates pro-tumorigenic pathways in ESCC cells.
- POSTN represents a promising novel therapeutic target for esophageal squamous cell carcinoma.
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