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Updated: Jul 2, 2025
A Preclinical Mouse Model of Osteosarcoma to Define the Extracellular Vesicle-mediated Communication Between Tumor and Mesenchymal Stem Cells
Published on: May 6, 2018
Enhancing anti-tumor potential: low-intensity vibration suppresses osteosarcoma progression and augments MSCs'
Xue Xiong1,2, Qingji Huo1,2, Kexin Li1,2
1Department of Pharmacology, School of Pharmacy, Harbin Medical University, Harbin 150081, China.
Abstract:
Rationale: Osteosarcoma (OS), a common malignant bone tumor, calls for the investigation of novel treatment strategies. Low-intensity vibration (LIV) presents itself as a promising option, given its potential to enhance bone health and decrease cancer susceptibility. This research delves into the effects of LIV on OS cells and mesenchymal stem cells (MSCs), with a primary focus on generating induced tumor-suppressing cells (iTSCs) and tumor-suppressive conditioned medium (CM). Methods: To ascertain the influence of vibration frequency, we employed numerical simulations and conducted experiments to determine the most effective LIV conditions. Subsequently, we generated iTSCs and CM through LIV exposure and assessed the impact of CM on OS cells. We also explored the underlying mechanisms of the tumor-suppressive effects of LIV-treated MSC CM, with a specific focus on vinculin (VCL). We employed cytokine array, RNA sequencing, and Western blot techniques to investigate alterations in cytokine profiles, transcriptomes, and tumor suppressor proteins. Results: Numerical simulations validated LIV frequencies within the 10-100 Hz range. LIV induced notable morphological changes in OS cells and MSCs, confirming its dual role in inhibiting OS cell progression and promoting MSC conversion into iTSCs. Upregulated VCL expression enhanced MSC responsiveness to LIV, significantly bolstering CM's efficacy. Notably, we identified tumor suppressor proteins in LIV-treated CM, including procollagen C endopeptidase enhancer (PCOLCE), histone H4 (H4), peptidylprolyl isomerase B (PPIB), and aldolase A (ALDOA). Consistently, cytokine levels decreased significantly in LIV-treated mouse femurs, and oncogenic transcript levels were downregulated in LIV-treated OS cells. Moreover, our study demonstrated that combining LIV-treated MSC CM with chemotherapy drugs yielded additive anti-tumor effects. Conclusions: LIV effectively impeded the progression of OS cells and facilitated the transformation of MSCs into iTSCs. Notably, iTSC-derived CM demonstrated robust anti-tumor properties and the augmentation of MSC responsiveness to LIV via VCL. Furthermore, the enrichment of tumor suppressor proteins within LIV-treated MSC CM and the reduction of cytokines within LIV-treated isolated bone underscore the pivotal tumor-suppressive role of LIV within the bone tumor microenvironment.
Insights
Low-intensity vibration (LIV) inhibits osteosarcoma progression and converts mesenchymal stem cells (MSCs) into tumor-suppressing cells (iTSCs). LIV-treated MSC-conditioned medium (CM) shows anti-tumor effects, enhanced by vinculin (VCL) and enriched with tumor suppressor proteins.
Area of Science:
- Biomedical Engineering
- Oncology
- Regenerative Medicine
Background:
- Osteosarcoma (OS) is a prevalent bone malignancy requiring novel therapeutic strategies.
- Low-intensity vibration (LIV) shows potential in bone health and cancer prevention.
- Mesenchymal stem cells (MSCs) can be modulated for therapeutic applications.
Purpose of the Study:
- To investigate the effects of LIV on osteosarcoma (OS) cells and MSCs.
- To generate induced tumor-suppressing cells (iTSCs) and tumor-suppressive conditioned medium (CM) using LIV.
- To explore the anti-tumor mechanisms of LIV-treated MSC-CM, focusing on vinculin (VCL).
Main Methods:
- Numerical simulations and experiments to determine optimal LIV frequencies (10-100 Hz).
- Generation of iTSCs and CM via LIV exposure; assessment of CM's impact on OS cells.
- Cytokine array, RNA sequencing, and Western blot to analyze molecular changes and protein expression.
Main Results:
- LIV induced morphological changes in OS cells and MSCs, inhibiting OS progression and promoting MSC to iTSC conversion.
- Upregulated VCL expression enhanced MSC responsiveness to LIV, increasing CM efficacy.
- LIV-treated CM contained tumor suppressor proteins (PCOLCE, H4, PPIB, ALDOA); cytokine levels decreased in vivo; oncogenic transcripts downregulated in OS cells. Combination therapy showed additive anti-tumor effects.
Conclusions:
- LIV effectively inhibits OS progression and facilitates MSCs' transformation into iTSCs.
- iTSC-derived CM exhibits significant anti-tumor properties, with VCL augmenting MSC responsiveness to LIV.
- Enrichment of tumor suppressor proteins in LIV-treated MSC-CM and reduced cytokines in vivo highlight LIV's role in the bone tumor microenvironment.
