Upstream Hedgehog Signaling Components are Exported in Exosomes of Cervical Cancer Cell Lines

Bhat, Anjali; Sharma, Aman; Bharti, Alok C.

doi:10.2217/nnm-2018-0143

Cited by 26 publications

(34 citation statements)

References 68 publications

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“…The release of Ptc containing EVs in disaggregated Cl8 wing disc cell culture reinforces the existence of an MVB-mediated process for extracellular targeting of Ptc. Accordingly, previous proteomic studies have found Ptc in EVs secreted by cultured mammary cancer cells (Bhat et al, 2018). The presence of Ptc in exosomes in tissue culture cells does not necessarily imply the release of Ptc in exosomes in the context of developing tissues.…”

Section: Discussionmentioning

confidence: 93%

Polarized sorting of Patched enables cytoneme‐mediated Hedgehog reception in the Drosophila wing disc

et al. 2020

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Hedgehog (Hh) signal molecules play a fundamental role in development, adult stem cell maintenance and cancer. Hh can signal at a distance, and we have proposed that its graded distribution across Drosophila epithelia is mediated by filopodia-like structures called cytonemes. Hh reception by Patched (Ptc) happens at discrete sites along presenting and receiving cytonemes, reminiscent of synaptic processes. Here, we show that a vesicle fusion mechanism mediated by SNARE proteins is required for Ptc placement at contact sites. Transport of Ptc to these sites requires multivesicular bodies (MVBs) formation via ESCRT machinery, in a manner different to that regulating Ptc/Hh lysosomal degradation after reception. These MVBs include extracellular vesicle (EV) markers and, accordingly, Ptc is detected in the purified exosomal fraction from cultured cells. Blockage of Ptc trafficking and fusion to basolateral membranes result in low levels of Ptc presentation for reception, causing an extended and flattened Hh gradient.

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Section: Discussionmentioning

confidence: 93%

Polarized sorting of Patched enables cytoneme‐mediated Hedgehog reception in the Drosophila wing disc

et al. 2020

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“…Exosomes originate from endosomes, short lipid bilayer-enclosed structure particles varying in length from 30–140 nm, which are a subset of extracellular vesicles derived from most cells 8. Besides, exosomes function as mediators of tumor cell interaction and long-range signaling effectors responsible for coordinating a variety of hallmarks implications in cancer, including tumor formation, development, metastasis, angiogenesis, tumor immunity and treatment resistance 9. Moreover, exosomes are secretory products from various types of cells under specific physiological or pathological conditions, which possess multiple functional proteins including miRNAs 10.…”

Section: Introductionmentioning

confidence: 99%

<p>Cervical Cancer Cells-Secreted Exosomal microRNA-221-3p Promotes Invasion, Migration and Angiogenesis of Microvascular Endothelial Cells in Cervical Cancer by Down-Regulating MAPK10 Expression</p>

Zhang

Yuan

et al. 2019

CMAR

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PurposeCervical cancer (CC) is recognized as a common cancer with a high risk worldwide. Exosomal microRNAs (miRNAs) have received attention for their increasing potentials in CC therapy. In this study, we identify the involvement of miR-221-3p in CC progression by affecting angiogenesis of microvascular endothelial cells (MVECs).MethodsMicroarray-based gene expression profiling was conducted to retrieve the differentially expressed genes in CC. The expression patterns of miR-221-3p were measured by RT-qPCR, while Western blot analysis and RT-qPCR were performed to determine the expression of MAPK10 in the CC tissues and cells, followed by verification of the interaction between miR-221-3p and MAPK10 using dual luciferase reporter gene assay. Then the effects of miR-221-3p and MAPK10 on cell activities were assessed through gain- and loss-of-function experiments in CC. Subsequently, the impact of exosomal miR-221-3p on MVEC proliferation, migration, invasion and angiogenesis was examined after exosomal isolation from CC cells and co-cultured with MVECs.ResultsGene expression profile showed that MAPK10 might participate in CC with a low expression. Moreover, miR-221-3p was highly expressed and MAPK10 was poorly expressed in CC tissues and cells. It was observed that miR-221-3p targeted MAPK10. Depletion of miR-221-3p blocked the cell proliferation, invasion and migration in CC by up-regulating MAPK10. Moreover, CC cells-derived exosomes carrying miR-221-3p accelerated MVEC proliferation, invasion, migration and angiogenesis in CC by regulating MAPK10.ConclusionCC cells-derived exosomes harboring miR-221-3p enhanced MVEC angiogenesis in CC by decreasing MAPK10.

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“…With the high mortality rate of cervical cancers, more information is needed regarding detection and treatment of the diseased. In this regard, several investigators have begun to examine extracellular vesicles (EVs) and their role in disease protection [2], as disease biomarkers [3][4][5] and/or as a cargo/vaccine agents for cervical cancer [6][7][8][9][10][11][12][13][14][15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

Alcohol Exposure Impacts the Composition of HeLa-Derived Extracellular Vesicles

et al. 2019

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Extracellular vesicles are nanosized vesicles that are under intense investigation for their role in intercellular communication. Extracellular vesicles have begun to be examined for their role in disease protection and their role as disease biomarkers and/or vaccine agents. The goal of this study was to investigate the effects of alcohol exposure on the biogenesis and composition of extracellular vesicles derived from the cervical cancer line, HeLa. The HeLa cells were cultured in exosome-free media and were either mock-treated (control) or treated with 50 mM or 100 mM of alcohol for 24 h and 48 h. Our results demonstrated that alcohol significantly impacts HeLa cell viability and exosome biogenesis/composition. Importantly, our studies demonstrate the critical role of alcohol on HeLa cells, as well as HeLa-derived extracellular vesicle biogenesis and composition. Specifically, these results indicate that alcohol alters extracellular vesicles’ packaging of heat shock proteins and apoptotic proteins. Extracellular vesicles serve as communicators for HeLa cells, as well as biomarkers for the initiation and progression of disease.

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Upstream Hedgehog Signaling Components are Exported in Exosomes of Cervical Cancer Cell Lines

Cited by 26 publications

References 68 publications

Polarized sorting of Patched enables cytoneme‐mediated Hedgehog reception in the Drosophila wing disc

Polarized sorting of Patched enables cytoneme‐mediated Hedgehog reception in the Drosophila wing disc

<p>Cervical Cancer Cells-Secreted Exosomal microRNA-221-3p Promotes Invasion, Migration and Angiogenesis of Microvascular Endothelial Cells in Cervical Cancer by Down-Regulating MAPK10 Expression</p>

Alcohol Exposure Impacts the Composition of HeLa-Derived Extracellular Vesicles

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