Extracellular vesicles from osteosarcoma cell lines contain miRNAs associated with cell adhesion and apoptosis

Jerez, Sofía; Araya, Héctor; Hevia, Daniel; Irarrázaval, Carlos E.; Thaler, Roman; Wijnen, André J. van; Galindo, Mario

doi:10.1016/j.gene.2019.06.005

Cited by 48 publications

(67 citation statements)

References 81 publications

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“…OS-derived exosomes from metastatic cells induced an increase in migration and invasion capacity of recipient osteoblasts compared to the uptake of non-metastatic OS-derived exosomes [100]. In agreement with previous data [99], the miRNA profile of exosomes from metastatic and non-metastatic OS cells differed, with an enrichment of target genes associated with metastasis and cancer. Amongst these, miR-675 was highly present in metastatic OS-derived exosomes.…”

Section: Exosomes In Ossupporting

confidence: 90%

“…Amongst the predicted target genes for the differential expressed miRNA, there was an enrichment of genes associated with tumour progression and metastasis. A deeper analysis of miRNAs enriched in exosomes from the most metastatic OS cell line (SAOS2) revealed that 4 miRNAs targeted 31 target genes from the same network associated with cellular adhesion and apoptosis [99]. Therefore, data from these studies suggest that OS-derived exosomes could drive a pro-metastatic phenotype by transferring specific proteins and miRNA to other OS cells, resulting in induction of changes in migration, adhesion, and angiogenesis.…”

Section: Exosomes In Osmentioning

confidence: 94%

“…Among the 250 most enriched proteins in exosomes, pathway analysis revealed an association with migration, adhesion, and angiogenesis, all important processes for cancer dissemination and modulation of the pre-metastatic niche. Following these data, the same group investigated the exosomal cargo of several OS cell lines [99]. A difference in the miRNA content was seen between metastatic and non-metastatic OS-derived exosomes.…”

Section: Exosomes In Osmentioning

confidence: 98%

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Exosomes in Bone Sarcomas: Key Players in Metastasis

Chicón-Bosch

Tirado

2020

Cells

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Bone sarcomas are rare cancers which often present with metastatic disease and are still associated with poor survival rates. Studies in the last decade have identified that exosomes, a type of extracellular vesicle released by cells, play an important role in tumour progression and dissemination. Through the transfer of their cargo (RNAs, proteins, and lipids) across cells, they are involved in cellular cross-talk and can induce changes in cellular behaviour. Exosomes have been shown to be important in metastasis organotropism, induction of angiogenesis and vascular permeability, the education of cells towards a pro-metastatic phenotype or the interaction between stromal and tumour cells. Due to the importance exosomes have in disease progression and the high incidence of metastasis in bone sarcomas, recent studies have evaluated the implications of these extracellular vesicles in bone sarcomas. In this review, we discuss the studies that evaluate the role of exosomes in osteosarcoma, Ewing sarcoma, and preliminary data on chondrosarcoma.

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Section: Exosomes In Ossupporting

confidence: 90%

Section: Exosomes In Osmentioning

confidence: 94%

Section: Exosomes In Osmentioning

confidence: 98%

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Exosomes in Bone Sarcomas: Key Players in Metastasis

Chicón-Bosch

Tirado

2020

Cells

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“…MVs were primarily regarded as unfunctional cellular components to be discarded, yet it has been increasingly suggested that MVs are important tools for the exchange of cellular information and materials, and closely correlated with tumor distant metastasis and immune inhibition (Steinbichler et al, 2017;Fan et al, 2018;Seo et al, 2018;Jerez et al, 2019). MVs are capable of inducing various biological processes after being transferred into recipient cells, such as angiogenesis, metastasis formation, therapeutic resistance, epithelial-mesenchymal transition (EMT) and epigenetic programming (Kreimer et al, 2015;Milane et al, 2015;Gopal et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

“…MVs derived from bone marrow mesenchymal stem cell (BMMSC) can promote tumorigenesis and development (Crompot et al, 2017;Boyiadzis and Whiteside, 2018). miRNAs in MVs, as post-transcriptional regulatory elements, directly regulate gene expression, target mRNA expression and translation or induce mRNA degradation to reduce protein synthesis by directly binding with the 3 ′ -untranslation region (3 ′ -UTR) of specific mRNA targets (Braicu et al, 2015;Jerez et al, 2019), ultimately induce multiple pathophysiological processes, such as leukemia stem cell formation, regulation of tumor cell proliferation, angiogenesis, invasion, metastasis, and immune escape to modulate leukemia development (Braicu et al, 2015;Del Principe et al, 2017). microRNAs (miRNA) are a class of evolutionarily conserved 22 to 24-nucleotide small RNAs in length, which are widely found in eukaryotic cells with molecular functions to regulate cell differentiation, proliferation and apoptosis (Summerer et al, 2013;Zheng et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

miR-221-3p Delivered by BMMSC-Derived Microvesicles Promotes the Development of Acute Myelocytic Leukemia

Zhang

Wang

et al. 2020

Front. Bioeng. Biotechnol.

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The study aims to investigate the effects of miR-221-3p in bone marrow mesenchymal stem cell (BMMSC)-derived microvesicles (MVs) on cell cycle, proliferation and invasion of acute myelocytic leukemia (AML). Methods: Bioinformatics was used to predict differentially expressed miRNAs (DEmiRNAs) in AML. The morphology of BMMSC-derived MVs was observed under an electron microscope, and the positional relation of MVs and OCI-AML2 cells was observed by a fluorescence microscope. MTT, Transwell, and flow cytometry assays were used to analyze the effects of MVs on OCI-AML2 cells. The targeted relationship between miR-221-3p and CDKN1C was detected by dual luciferase assay. Results: It was verified that miR-221-3p promoted the proliferation, invasion and migration of OCI-AML2 cells, and induced the cell cycle arrest in G1/S phase as well as inhibited cell apoptosis. Further studies showed that MVs promoted the proliferation, migration and invasion of AML, and induced the cell cycle arrest in G1/S phase through miR-221-3p. It was confirmed that miR-221-3p can directly target CDKN1C to regulate cell cycle, proliferation and invasion of AML. Conclusion: miR-221-3p in BMMSC-derived MVs regulated AML cell cycle, cell proliferation and invasion through targeting CDKN1C. miR-221-3p and CDKN1C were considered to be potential targets and biomarkers for the treatment of AML in clinic.

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Osteosarcoma‐Derived Exosomes as Potential PET Imaging Nanocarriers for Lung Metastasis

Almeida

Fonseca

Ferreira

et al. 2022

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Lung metastases represent the most adverse clinical factor and rank as the leading cause of osteosarcoma‐related death. Nearly 80% of patients present lung micrometastasis at diagnosis not detected with current clinical tools. Herein, an exosome (EX)‐based imaging tool is developed for lung micrometastasis by positron emission tomography (PET) using osteosarcoma‐derived EXs as natural nanocarriers of the positron‐emitter copper‐64 (64Cu). Exosomes are isolated from metastatic osteosarcoma cells and functionalized with the macrocyclic chelator NODAGA for complexation with 64Cu. Surface functionalization has no effect on the physicochemical properties of EXs, or affinity for donor cells and endows them with favorable pharmacokinetics for in vivo studies. Whole‐body PET/magnetic resonance imaging (MRI) images in xenografted models show a specific accumulation of 64Cu‐NODAGA‐EXs in metastatic lesions as small as 2–3 mm or in a primary tumor, demonstrating the exquisite tropism of EXs for homotypic donor cells. The targetability for lung metastasis is also observed by optical imaging using indocyanine green (ICG)‐labeled EXs and D‐luciferin‐loaded EXs. These findings show that tumor‐derived EXs hold great potential as targeted imaging agents for the noninvasive detection of small lung metastasis by PET. This represents a step forward in the biomedical application of EXs in imaging diagnosis with increased translational potential.

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Extracellular vesicles from osteosarcoma cell lines contain miRNAs associated with cell adhesion and apoptosis

Cited by 48 publications

References 81 publications

Exosomes in Bone Sarcomas: Key Players in Metastasis

Exosomes in Bone Sarcomas: Key Players in Metastasis

miR-221-3p Delivered by BMMSC-Derived Microvesicles Promotes the Development of Acute Myelocytic Leukemia

Osteosarcoma‐Derived Exosomes as Potential PET Imaging Nanocarriers for Lung Metastasis

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