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Updated: Sep 16, 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
Human osteosarcoma cell secretome impairs neonatal mouse calvarial osteogenic cells functions and modifies the
Argia Ucci1, Luca Giacchi1, Maria Concetta Cufaro2
1Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.
Abstract:
Osteosarcoma is the most common pediatric primary bone tumor, whose growth strictly relies on a complex interplay among tumor cells, resident cells, and the bone matrix. We investigated the effects of secretome collected from the human osteosarcoma cell line MNNG/HOS on mouse primary osteogenic cells, finding that prolonged exposure alters osteoblast phenotype and activity. MNNG/HOS secretome also reduces the production and release of collagen type I, the most abundant constituent of the bone matrix, and hinders osteoblast ability to form nodule of mineralization, compared to osteogenic cells treated with their own secretome. Given the crucial role exerted by secretome on tumor growth, we aimed also to determine whether osteosarcoma cells secretome can influence the osteoblast release of extracellular nanoparticles (NPs) as well as NPs protein cargo. Intriguingly, we found that MNNG/HOS secretome exerts a direct effect on osteoblast-NPs, reprogramming their protein cargo and subsequently influencing extracellular matrix composition and collagen formation, in favor of tumor progression. Overall, our findings indicate the ability of MNNG/HOS cells to fuel their own malignancy by deranging bone matrix composition and stimulating osteoblast-nanoparticles shuttling of osteosarcoma promoting factors.
Insights
Osteosarcoma cells release factors that change bone cells, reduce collagen, and alter nanoparticles. This promotes tumor growth by disrupting the bone matrix and aiding cancer progression.
Area of Science:
- Oncology
- Biochemistry
- Cell Biology
Background:
- Osteosarcoma, a primary bone tumor in children, depends on interactions between tumor cells, resident cells, and the bone matrix.
- The tumor microenvironment significantly influences osteosarcoma progression.
Purpose of the Study:
- To investigate the impact of osteosarcoma cell secretome on osteoblast function and extracellular matrix.
- To determine if osteosarcoma secretome influences osteoblast-derived extracellular nanoparticles (NPs) and their protein cargo.
Main Methods:
- Collected secretome from the human osteosarcoma cell line MNNG/HOS.
- Treated mouse primary osteogenic cells with MNNG/HOS secretome.
- Analyzed changes in osteoblast phenotype, collagen type I production, mineralization, and osteoblast-derived NPs.
Main Results:
- MNNG/HOS secretome altered osteoblast phenotype and activity.
- Reduced collagen type I production and hindered mineralization in treated osteoblasts.
- Reprogrammed protein cargo of osteoblast-derived NPs, influencing extracellular matrix composition.
Conclusions:
- Osteosarcoma cells can manipulate the bone microenvironment to favor tumor progression.
- Secretome-mediated reprogramming of osteoblast-derived NPs facilitates the shuttling of tumor-promoting factors.
- This highlights a mechanism by which osteosarcoma fuels its own malignancy.
