Work

Radiation-Induced EMT of Adipose-Derived Stem Cells in 3D Organotypic Culture via Notch Signaling Pathway

Year: 2025

Type: article

Abstract: In our previous study, adipose-derived stem cells (ASCs) cultured in a three-dimensional (3D) organotypic system exhibited mesenchymal-to-epithelial transition (MET) features, including cobblestone morphology and increased expression of E-cadherin and CK18. In this study, we investigated whether ionizing radiation could reverse this phenotype via epithelial–mesenchymal transition (EMT) and examined the involvement of Notch signaling. Mouse ASCs were cultured in Matrigel-based 3D organotypic conditions and exposed to 8 Gy of γ-radiation, and EMT- and Notch-related gene and protein expression were assessed 96 h post-irradiation using ATP viability assays, RT-qPCR, and Western blotting. Exposure to 8 Gy significantly reduced cell viability in 2D ASCs to 49.50 ± 6.50% compared with 61.02 ± 5.77% in 3D organoids (p < 0.0001). Irradiated 3D organoids showed EMT-like changes, including an increase of ~2.5-fold in fibronectin and an increase of ~2.0-fold in Twist1 expression, while epithelial CK18 was modestly elevated. Notch signaling was concurrently activated, with Notch1 and Jagged1 increasing by more than twofold and Fra-1 being significantly upregulated. Pretreatment with 20 μM of the γ-secretase inhibitor (GSI) kept cell viability above 90% and suppressed radiation-induced fibronectin, Twist1, Notch1, and Jagged1 expression. These findings indicate that ionizing radiation promotes EMT in 3D-cultured ASCs and reverses prior epithelialization, with Notch signaling playing a key regulatory role. The 3D ASC organoid model may thus provide a physiologically relevant platform for investigating radiation-induced plasticity and potential antifibrotic interventions.

Source: Biology

DOI: 10.3390/biology14091306

Authors: Seon Jeong Choi, Meesun Kim, Kyung Tae Chung, Tae Gen Son

Institutions: Dong-Eui University, Dongnam Institute of Radiological & Medical Sciences

Language: English

Topic: Cancer Cells and Metastasis

Subfield: Oncology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,258