Functions and therapeutic potentials of exosomes in osteosarcoma

Yue, Jiaji; Chen, Zhe‐Sheng; Xu, Xiaojin; Li, Shenglong

doi:10.15212/amm-2022-0024

Cited by 12 publications

(5 citation statements)

References 104 publications

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“…At present, the common treatment options such as radiotherapy, chemotherapy and surgery have not achieved satisfactory clinical results [ 19 ]. Cellular immunotherapy, stem cell therapy, and targeted therapy have been used in patients with recurrent OS in recent years [ 20 , 21 ]. Tumor immunotherapy plays an anti-tumor role by stimulating and enhancing the immune response of the body.…”

Section: Discussionmentioning

confidence: 99%

What role does GPR65 play in the progression of osteosarcoma? Its mechanism and clinical significance

Qi,

Liu,

Zhang

2024

Cancer Cell Int

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Background GPR65 is a pH-sensing G-protein-coupled receptor that acts as a key innate immune checkpoint in the human tumor microenvironment, inhibiting the release of inflammatory factors and inducing significant upregulation of tissue repair genes. However, the expression pattern and function of GPR65 in osteosarcoma (OS) remain unclear. The purpose of this study was to investigate and elucidate the role of GPR65 in the microenvironment, proliferation and migration of OS. Methods Retrospective RNA-seq data analysis was conducted in a cohort of 97 patients with OS data in the TAEGET database. In addition, single-cell sequencing data from six surgical specimens of human OS patients was used to analyze the molecular evolution process during OS genesis. Tissues chips and bioinformatics results were used to verify GPR65 expression level in OS. MTT, colony formation, EdU assay, wound healing, transwell assay and F-actin assay were utilized to analyze cell proliferation and invasion of OS cancer cells. RNA-seq was used to explore the potential mechanism of GPR65’s role in OS. Results GPR65 expression was significantly low in OS, and subgroup analysis found that younger OS patients, OS patients in metastatic status, and overall survival and progression free survival OS patients had lower GPR65 expression. From ScRNA-seq data of GSE162454, we found the expression of GPR65 is significantly positively correlated with CD4 + T cells CD8 + T cells and OS related macrophage infiltration. Verification experiment found that silencing the expression of GPR65 in osteosarcoma cells U2OS and HOS could promote the proliferation and invasion process, RNA-seq results showed that the role of GPR65 in OS cells was related to immune system, metabolism and signal transduction. Conclusion The low expression of GPR65 in OS leads to high metastasis rate and poor prognosis in OS patients. The suppression of immune escape and inhibition of proliferation may be a key pathway for GPR65 to participate in the progression of OS. The current study strengthens the role of GPR65 in OS development and provides a potential biomarker for the prognosis of OS patients.

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Section: Discussionmentioning

confidence: 99%

What role does GPR65 play in the progression of osteosarcoma? Its mechanism and clinical significance

Qi,

Liu,

Zhang

2024

Cancer Cell Int

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“…M1 macrophages often propel the inflammatory and fibrotic processes by releasing pro-fibrotic mediators such as transforming growth factor-beta1, directly activating fibroblasts and modulating extracellular matrix turnover [ 26 , 35 , 54 , 55 ]. Conversely, M2 macrophages are implicated in the anti-inflammatory responses and tissue repair, demonstrating their potential in therapeutic strategies for fibrotic diseases [ 12 , 56 , 57 ]. Exosomes, the potent modulators of macrophage polarization, can be applied in innovative therapeutic approaches.…”

Section: Discussionmentioning

confidence: 99%

Endothelial cells-derived exosomes-based hydrogel improved tendinous repair via anti-inflammatory and tissue regeneration-promoting properties

Dou,

Zhai,

et al. 2024

J Nanobiotechnol

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Tendon injuries are common orthopedic ailments with a challenging healing trajectory, especially in cases like the Achilles tendon afflictions. The healing trajectory of tendon injuries is often suboptimal, leading to scar formation and functional impairment due to the inherent low metabolic activity and vascularization of tendon tissue. As pressing is needed for effective interventions, efforts are made to explore biomaterials to augment tendon healing. However, tissue engineering approaches face hurdles in optimizing tissue scaffolds and nanomedical strategies. To navigate these challenges, an injectable hydrogel amalgamated with human umbilical vein endothelial cells-derived exosomes (HUVECs-Exos) was prepared and named H-Exos-gel in this study, aiming to enhance tendon repair. In our research involving a model of Achilles tendon injuries in 60 rats, we investigated the efficacy of H-Exos-gel through histological assessments performed at 2 and 4 weeks and behavioral assessments conducted at the 4-week mark revealed its ability to enhance the Achilles tendon’s mechanical strength, regulate inflammation and facilitate tendon regeneration and functional recovery. Mechanically, the H-Exos-gel modulated the cellular behaviors of macrophages and tendon-derived stem cells (TDSCs) by inhibiting inflammation-related pathways and promoting proliferation-related pathways. Our findings delineate that the H-Exos-gel epitomizes a viable bioactive medium for tendon healing, heralding a promising avenue for the clinical amelioration of tendon injuries.

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“…In addition to the use of bioactive molecules to regulate ncRNAs, ncRNA inhibitors or mimics can also be supplied to target cells via liposomes or nanoparticle delivery systems, with the goal of restoring or enhancing the tumor suppressor function of ncRNAs. Extracellular vesicles, which can exist steadily and perform a variety of functions in the TME and immunological infiltration, are one of the main delivery substances in liposomes (Gao et al, 2022; Guo et al, 2023; Li, 2021; Yue et al, 2022). Specifically, extracellular nanovesicles circ‐0000190 in OS cells show the ability to boost miR‐767‐5p to control TET 1 and limit the growth of OS as well as weaken OS cell motility, proliferation, and invasion (Li, Pei, et al, 2020).…”

Section: The Promising Roles Of Targeting Ncrnas In Os Therapymentioning

confidence: 99%

Deciphering chemoresistance in osteosarcoma: Unveiling regulatory mechanisms and function through the lens of noncoding RNA

Chen,

Gong,

Zhou

et al. 2024

Drug Development Research

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Osteosarcoma (OS) is a primary malignant bone tumor and is prevalent in children, adolescents, and elderly individuals. It has the characteristics of high invasion and metastasis. Neoadjuvant chemotherapy combined with surgical resection is the most commonly used treatment for OS. However, the efficacy of OS is considerably diminished by chemotherapy resistance. In recent years, noncoding RNAs (ncRNAs), including microRNAs, long noncoding RNAs, and circular RNAs, are hot topics in the field of chemotherapy resistance research. Several studies have demonstrated that ncRNAs are substantially associated with chemoresistance in OS. Thus, the present study overviews the abnormally expressed ncRNAs in OS and the molecular mechanisms involved in chemoresistance, with an emphasis on their function in promoting or inhibiting chemoresistance. ncRNAs are expected to become potential therapeutic targets for overcoming drug resistance and predictive biomarkers in OS, which are of great significance for enhancing the therapeutic effect and improving the prognosis.

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Functions and therapeutic potentials of exosomes in osteosarcoma

Cited by 12 publications

References 104 publications

What role does GPR65 play in the progression of osteosarcoma? Its mechanism and clinical significance

What role does GPR65 play in the progression of osteosarcoma? Its mechanism and clinical significance

Endothelial cells-derived exosomes-based hydrogel improved tendinous repair via anti-inflammatory and tissue regeneration-promoting properties

Deciphering chemoresistance in osteosarcoma: Unveiling regulatory mechanisms and function through the lens of noncoding RNA

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