Targeting MDA‐MB‐231 Cancer Stem Cells With Temsirolimus in 3D Collagen/PGA/Na2SiO3‐Based Bone Model
Abstract This study evaluated the efficacy of temsirolimus in a 3D model mimicking breast cancer stem cell (CSC) metastasis to bone. A composite material (collagen/PGA/Na₂SiO₃) is used to create a scaffold with bone marrow mesenchymal stem cells (BM‐MSCs) and human umbilical vein endothelial cells (...
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| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley-VCH
2025-04-01
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| Series: | Macromolecular Materials and Engineering |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/mame.202400360 |
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| Summary: | Abstract This study evaluated the efficacy of temsirolimus in a 3D model mimicking breast cancer stem cell (CSC) metastasis to bone. A composite material (collagen/PGA/Na₂SiO₃) is used to create a scaffold with bone marrow mesenchymal stem cells (BM‐MSCs) and human umbilical vein endothelial cells (HUVECs). MSCs maintained over 80% viability for 21 days on the scaffold. Calcium analysis shows increased calcium release in both control (3‐fold, 2.7‐fold) and osteogenic (2.3‐fold, 2.5‐fold) mediums on days 14 and 21. Gene expression analysis reveals higher levels of Osteopontin (OPN) (6‐fold), Osteocalcin (OCN) (12‐fold), and RUNX Family transcription factor 2 (RUNX2) (1.8‐fold) in the osteogenic medium (p < 0.05). The impact of 5 µM temsirolimus treatment for 6 hours is assessed under control and dynamic culture conditions, reducing mammalian target of rapamycin (mTOR)‐related protein levels (phospho (p)‐mTOR and p‐AKT) in CSCs. The composite material is characterized through viscosity and compression testing, confirming its suitability for supporting osteogenic differentiation and cell viability (WST‐1, Alizarin Red Staining, Calcium Assay, RT‐qPCR). Gene expression of CSCs, selected based on CD133 expression, shows elevated stemness‐associated genes (OCT4, NANOG), EMT (MMP2, CXCR4, CDH1, CDH2), and drug resistance (ABCG1, ABCG2) in the CD133⁺ group in dynamic condition. Temsirolimus treatment reduces the expression of these genes by 21‐fold to 7.52‐fold (p < 0.05). These findings suggest temsirolimus as a promising therapeutic for CSC metastasis to bone. [Correction added on April 8, 2025, after first online publication: the word CHD is updated to CDH in this version.] |
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| ISSN: | 1438-7492 1439-2054 |