Bone Marrow Mesenchymal Stem Cells-Derived Extracellular Vesicles Promote Proliferation, Invasion and Migration of Osteosarcoma Cells via the lncRNA MALAT1/miR-143/NRSN2/Wnt/β-Catenin Axis

Li, Fujiang; Chen, Xin; Shang, Cong; Ying, Qinglong; Zhou, Xihui; Zhu, Rongkun; Lu, Hongting; Hao, Xiwei; Dong, Qi; Jiang, Zhong

doi:10.2147/ott.s283459

Cited by 28 publications

(28 citation statements)

References 37 publications

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“…BMSCs, the OS precursor cells, participate in OS progression through cell-to-cell interactions [ 20 ]. BMSC exosomes play important roles in this process, but the specific mechanism remains unclear.…”

Section: Resultsmentioning

confidence: 99%

“…BMSCs promote the development of breast cancer and prostate cancer [ 17 ], yet inhibit the progression of glioblastoma and hepatocellular carcinoma [ 18 , 19 ]. Moreover, OS cells may originate from BMSCs, while BMSCs regulate OS metastasis [ 20 ]. However, the mechanism by which BMSCs regulate the malignant progression of OS remains unclear.…”

Section: Introductionmentioning

confidence: 99%

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Exosomal transfer of miR-769-5p promotes osteosarcoma proliferation and metastasis by targeting DUSP16

et al. 2021

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Background Osteosarcoma (OS) is a malignant tumor originating from mesenchymal stem cells, and has an extremely high fatality rate and ability to metastasize. Although mounting evidence suggests that miR-769-5p is strongly associated with the malignant progression and poor prognosis of various tumors, the exact role of miR-769-5p in OS is still unclear. Therefore, this study aimed to explore the relationship between miR-769-5p and the malignant progression of OS, and its underlying mechanism of action. Methods miR-769-5p expression was analyzed in GSE28423 from the GEO database and measured in OS clinical specimens and cell lines. The effects of miR-769-5p on OS proliferation, migration and invasion were measured both in vivo and in vitro. In addition, bioinformatics analyses and luciferase reporter assays were used to explore the target genes of miR-769-5p. Rescue experiments were also conducted. Moreover, a co-culture model was used to test the cell interaction between bone mesenchymal stem cells (BMSC) and OS cells. Results We found that miR-769-5p is highly expressed in OS clinical specimens and cell lines. In vivo and in vitro experiments also showed that miR-769-5p significantly promoted the proliferation, migration and invasion of OS cells. Dual-specific phosphatase 16 (DUSP16) was negatively associated with miR-769-5p expression in OS cells and tissue samples and was validated as the downstream target by luciferase reporter assay and western blotting. Rescue experiments showed that DUSP16 reverses the effect of miR-769-5p on OS cells by negatively regulating the JNK/p38 MAPK signaling pathway. Additionally, the results of the co-culture of BMSCs and OS cells confirmed that miR-769-5p was transferred from BMSCs to OS cells through exosomes. Conclusions In summary, this study demonstrates for the first time that BMSC-derived exosomal miR-769-5p promotes OS proliferation and metastasis by targeting DUSP16 and activating the JNK/p38 MAPK signaling pathway, which could provide rationale for a new therapeutic strategy for OS.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Exosomal transfer of miR-769-5p promotes osteosarcoma proliferation and metastasis by targeting DUSP16

et al. 2021

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“…Caution must be practised however, as the protection afforded to other cells by MSCs and their EVs can have a negative effect in cancer. For example, Li and colleagues showed that EVs from bone marrow-derived MSCs can enhance osteosarcoma cell proliferation, invasion and migration in a mechanism involving the Wnt-B-catenin signaling [215]. Furthermore, Guo and colleagues showed that MSC-derived EVs containing miR-130b-3p promotes the progression of lung cancer [216].…”

Section: Mesenchymal Stem Cell-derived Extracellular Vesiclesmentioning

confidence: 99%

Recent Trends in Multipotent Human Mesenchymal Stem/Stromal Cells: Learning from History and Advancing Clinical Applications

Dzobo

2021

OMICS: A Journal of Integrative Biology

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Early reports demonstrated the presence of cells with stem-like properties in bone marrow, with these cells having both hematopoietic and mesenchymal lineages. Over the years, various investigations have purified and characterized mesenchymal stromal/stem cells (MSCs) from different human tissues as cells with multi-lineage differentiation potential under the appropriate conditions. Due to their appealing characteristics and potential, MSCs are leveraged in many applications including medicine, oncology, bioprinting and as recent as treatment of COVID-19. To date, reports indicate mesenchymal stromal/stem cells have varied differentiation capabilities into different cell types and demonstrate immunomodulating and antiinflammatory properties. Reports indicate that different MSCs microenvironments or niche and the resulting heterogeneity may influence their behavior and differentiation capacity. The potential clinical applications of mesenchymal stromal/stem cells have led to an avalanche of research reports on their properties and hundreds of clinical trials being undertaken. The future looks bright and promising for mesenchymal stem cell research with many clinical trials under way to prove their utility in many applications and in the clinic. This report provides an update on the potential broader use of mesenchymal stromal/stem cells, review early observations of the presence of these cells in the bone marrow and their magnificent differentiation capabilities and immunomodulation.

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“…Electron microscopic examination revealed the presence of EVs of 50-200 nm in diameter that derive from bone and tumor cells. MSC-derived exosomes can promote cell proliferation, migration and invasion in osteosarcoma in vitro and in vivo [78,79]. Moreover, MSC-EVs can also promote autophagy contributing to MSC-EV-induced promotion of malignant tumorigenesis [78].…”

Section: Role Of Evs In Osteosarcoma Microenvironment and Tumoral Growthmentioning

confidence: 99%

Extracellular Vesicles in Osteosarcoma: Antagonists or Therapeutic Agents?

Martino

Rossi

Battafarano

et al. 2021

IJMS

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Osteosarcoma (OS) is a skeletal tumor affecting mainly children and adolescents. The presence of distance metastasis is frequent and it is localized preferentially to the lung, representing the main reason for death among patients. The therapeutic approaches are based on surgery and chemotherapeutics. However, the drug resistance and the side effects associated with the chemotherapy require the identification of new therapeutic approaches. The understanding of the complex biological scenario of the osteosarcoma will open the way for the identification of new targets for its treatment. Recently, a great interest of scientific community is for extracellular vesicles (EVs), that are released in the tumor microenvironment and are important regulators of tumor proliferation and the metastatic process. At the same time, circulating extracellular vesicles can be exploited as diagnostic and prognostic biomarkers, and they can be loaded with drugs as a new therapeutic approach for osteosarcoma patients. Thus, the characterization of OS-related EVs could represent a way to convert these vesicles from antagonists for human health into therapeutic and/or diagnostic agents.

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Bone Marrow Mesenchymal Stem Cells-Derived Extracellular Vesicles Promote Proliferation, Invasion and Migration of Osteosarcoma Cells via the lncRNA MALAT1/miR-143/NRSN2/Wnt/β-Catenin Axis

Cited by 28 publications

References 37 publications

Exosomal transfer of miR-769-5p promotes osteosarcoma proliferation and metastasis by targeting DUSP16

Exosomal transfer of miR-769-5p promotes osteosarcoma proliferation and metastasis by targeting DUSP16

Recent Trends in Multipotent Human Mesenchymal Stem/Stromal Cells: Learning from History and Advancing Clinical Applications

Extracellular Vesicles in Osteosarcoma: Antagonists or Therapeutic Agents?

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