Exosomes in developmental signalling

McGough, Ian J.; Vincent, Jean‐Paul

doi:10.1242/dev.126516

Cited by 179 publications

(147 citation statements)

References 151 publications

(196 reference statements)

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“…Exosomes have been implicated in the secretion, diffusion and signal transduction of the class of lipid-modified ligand, those of the Hedgehog family of secreted proteins [40]. Gradilla et al regarded a functional Hedgehog associated to heterogeneous exosomes, either originated from exosomes or/and directly shedding from the plasma membrane of cytonemes, and that are essential for Hedgehog gradient formation [28].…”

Section: Discussionmentioning

confidence: 99%

Exosomes Derived from Human Bone Marrow Mesenchymal Stem Cells Promote Tumor Growth Through Hedgehog Signaling Pathway

Qi¹,

Zhou²,

Zhang³

et al. 2017

Cell Physiol Biochem

158

103

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Background/Aims: Mesenchymal stem/stromal cells (MSCs) are known to home to sites of tumor microenvironments where they participate in the formation of the tumor microenvironment and to interplay with tumor cells. However, the potential functional effects of MSCs on tumor cell growth are controversial. Here, we, from the view of bone marrow MSC-derived exosomes, study the molecular mechanism of MSCs on the growth of human osteosarcoma and human gastric cancer cells. Methods: MSCs derived from human bone marrow (hBMSCs) were isolated and cultured in complete DMEM/F12 supplemented with 10% exosome-depleted fetal bovine serum and 1% penicillin-streptomycin, cell culture supernatants containing exosomes were harvested and exosome purification was performed by ultracentrifugation. Osteosarcoma (MG63) and gastric cancer (SGC7901) cells, respectively, were treated with hBMSC-derived exosomes in the presence or absence of a small molecule inhibitor of Hedgehog pathway. Cell viability was measured by transwell invasion assay, scratch migration assay and CCK-8 test. The expression of the signaling molecules Smoothened, Patched-1, Gli1 and the ligand Shh were tested by western blot and RT-PCR. Results: In this study, we found that hBMSC-derived exosomes promoted MG63 and SGC7901 cell growth through the activation of Hedgehog signaling pathway. Inhibition of Hedgehog signaling pathway significantly suppressed the process of hBMSC-derived exosomes on tumor growth. Conclusion: Our findings demonstrated the new roles of hedgehog signaling pathway in the hBMSCs-derived exosomes induced tumor progression.

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Section: Discussionmentioning

confidence: 99%

Exosomes Derived from Human Bone Marrow Mesenchymal Stem Cells Promote Tumor Growth Through Hedgehog Signaling Pathway

Qi¹,

Zhou²,

Zhang³

et al. 2017

Cell Physiol Biochem

158

103

View full text Add to dashboard Cite

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“…Extracellular vesicle secretion involves 2 processes: the formation process, and the release process . Studies have shown that the RAB GTPase proteins are important regulators of intracellular vesicle transport, regulating vesicle trafficking at different stages, such as vesicle budding, vesicle and organelle flow, vesicle and accurate convergence, and fusion of cell membranes .…”

Section: Discussionmentioning

confidence: 99%

“…Extracellular vesicle secretion involves 2 processes: the formation process, and the release process. 26 Studies have shown that the RAB GTPase proteins are important regulators of intracellular vesicle transport, regulating vesicle trafficking at different stages, such as vesicle budding, vesicle and organelle flow, vesicle and accurate convergence, and fusion of cell membranes. 27,28 Sorting of cargo into EVs is a key step in the formation of EVs, which is regulated by a series of molecules, including endosomal sorting complex required for transport (ESCRT), 4 transmembrane protein CD63, and liposomes.…”

Section: Discussionmentioning

confidence: 99%

Epstein‐Barr virus‐encoded latent membrane protein 1 promotes extracellular vesicle secretion through syndecan‐2 and synaptotagmin‐like‐4 in nasopharyngeal carcinoma cells

et al. 2020

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Increasing evidence indicates that extracellular vesicles (EVs) play an important role in cancer cell‐to‐cell communication. The Epstein‐Barr virus (EBV)‐encoded latent membrane protein 1 (LMP1), which is closely associated with nasopharyngeal carcinoma (NPC) pathogenesis, can trigger multiple cell signaling pathways that affect cell progression. Several reports have shown that LMP1 promotes EV secretion, and LMP1 trafficking by EVs can enhances cancer progression and metastasis. However, the molecular mechanism by which LMP1 promotes EV secretion is not well understood. In the present study, we found that LMP1 promotes EV secretion by upregulated syndecan‐2 (SDC2) and synaptotagmin‐like‐4 (SYTL4) through nuclear factor (NF)‐κB signaling in NPC cells. Further study indicated that SDC2 interacted with syntenin, which promoted the formation of the EVs, and SYTL4 is associated with the release of EVs. Moreover, we found that stimulation of EV secretion by LMP1 can enhance the proliferation and invasion ability of recipient NPC cells and tumor growth in vivo. In summary, we found a new mechanism by which LMP1 upregulates SDC2 and SYTL4 through NF‐κB signaling to promote EV secretion, and further enhance cancer progression of NPC.

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“…Gradilla and co-workers showed that the transport of the morphogen hedgehog (Hh) is important for proper spatially restricted signalling during development [5]. The involvement of EVs in the developmental signalling was recently reviewed [6]. EVs secreted by cells present in a mature kidney were identified by studying urine samples.…”

Section: Introductionmentioning

confidence: 99%

Exosomes as secondary inductive signals involved in kidney organogenesis

Krause

Rak-Raszewska

Naillat

et al. 2018

J of Extracellular Vesicle

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The subfraction of extracellular vesicles, called exosomes, transfers biological molecular information not only between cells but also between tissues and organs as nanolevel signals. Owing to their unique properties such that they contain several RNA species and proteins implicated in kidney development, exosomes are putative candidates to serve as developmental programming units in embryonic induction and tissue interactions. We used the mammalian metanephric kidney and its nephron-forming mesenchyme containing the nephron progenitor/stem cells as a model to investigate if secreted exosomes could serve as a novel type of inductive signal in a process defined as embryonic induction that controls organogenesis. As judged by several characteristic criteria, exosomes were enriched and purified from a cell line derived from embryonic kidney ureteric bud (UB) and from primary embryonic kidney UB cells, respectively. The cargo of the UB-derived exosomes was analysed by qPCR and proteomics. Several miRNA species that play a role in Wnt pathways and enrichment of proteins involved in pathways regulating the organization of the extracellular matrix as well as tissue homeostasis were identified. When labelled with fluorescent dyes, the uptake of the exosomes by metanephric mesenchyme (MM) cells and the transfer of their cargo to the cells can be observed. Closer inspection revealed that besides entering the cytoplasm, the exosomes were competent to also reach the nucleus. Furthermore, fluorescently labelled exosomal RNA enters into the cytoplasm of the MM cells. Exposure of the embryonic kidney-derived exosomes to the whole MM in an ex vivo organ culture setting did not lead to an induction of nephrogenesis but had an impact on the overall organization of the tissue. We conclude that the exosomes provide a novel signalling system with an apparent role in secondary embryonic induction regulating organogenesis.

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Exosomes in developmental signalling

Cited by 179 publications

References 151 publications

Exosomes Derived from Human Bone Marrow Mesenchymal Stem Cells Promote Tumor Growth Through Hedgehog Signaling Pathway

Exosomes Derived from Human Bone Marrow Mesenchymal Stem Cells Promote Tumor Growth Through Hedgehog Signaling Pathway

Epstein‐Barr virus‐encoded latent membrane protein 1 promotes extracellular vesicle secretion through syndecan‐2 and synaptotagmin‐like‐4 in nasopharyngeal carcinoma cells

Exosomes as secondary inductive signals involved in kidney organogenesis

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