Exosomes as Biomarker Enriched Microvesicles: Characterization of Exosomal Proteins Derived from a Panel of Prostate Cell Lines with Distinct AR Phenotypes

Hosseini‐Beheshti, Elham; Pham, Steven; Adomat, Hans; Li, Na; Guns, Emma S. Tomlinson

doi:10.1074/mcp.m111.014845

Cited by 195 publications

(167 citation statements)

References 93 publications

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“…The mass spectrometry analysis of ATX complexes that had been isolated from exosomes additionally identified nidogen-2, agrin and seven laminin subunits, these together with perlecan are components of the extracellular matrix and the basement membrane. Agrin and laminin subunits have previously been detected using a proteomic approach to analyse exosomes, such as those produced by prostate cancer cells (Hosseini-Beheshti et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Exosomes bind to autotaxin and act as a physiological delivery mechanism to stimulate LPA receptor signalling in cells

Jethwa

Leah

Zhang

et al. 2016

Journal of Cell Science

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Autotaxin (ATX; also known as ENPP2), the lysophospholipase responsible for generating the lipid receptor agonist lysophosphatidic acid (LPA), is a secreted enzyme. Here we show that, once secreted, ATX can bind to the surface of cell-secreted exosomes. Exosomebound ATX is catalytically active and carries generated LPA. Once bound to a cell, through specific integrin interactions, ATX releases the LPA to activate cell surface G-protein-coupled receptors of LPA; inhibition of signalling by the receptor antagonist Ki1642 suggests that these receptors are LPAR1 and LPAR3. The binding stimulates downstream signalling, including phosphorylation of AKT and mitogenactivated protein kinases, the release of intracellular stored Ca 2+ and cell migration. We propose that exosomal binding of LPA-loaded ATX provides a means of efficiently delivering the lipid agonist to cell surface receptors to promote signalling. We further propose that this is a means by which ATX-LPA signalling operates physiologically.

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Section: Discussionmentioning

confidence: 99%

Exosomes bind to autotaxin and act as a physiological delivery mechanism to stimulate LPA receptor signalling in cells

Jethwa

Leah

Zhang

et al. 2016

Journal of Cell Science

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“…[1][2][3] At first, the inward budding of late endosomes formed multivesicular endosomes, which then fused with the outer cell membrane, and finally, the exosomes packaged in multivesicular endosomes are released outside. 4 It has been widely accepted that exosomes can exist in many kinds of body fluids, physiologically and pathologically, including plasma, urine, saliva, and malignant effusions. 5 Studies reported that exosomes can be found in the culture supernatant of many different types of cells, such as normal cells (e.g.…”

Section: Introductionmentioning

confidence: 99%

Characterization of exosomal RNAs derived from human gastric cancer cells by deep sequencing

Ren

Zhou

et al. 2017

Tumour Biol.

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Exosomes secreted from the cell to the extracellular environment play an important role in intercellular communication.Next-generation sequencing technology, which has achieved great development recently, allows us to detect more complete data and gain even deeper analyses of RNA transcriptomes. In our research, we extracted exosomes from different gastric cancer cell lines and immortalized normal gastric mucosal epithelial cell line and examined the amounts of exosomal proteins and RNAs. Our data showed that the secreted amount of cancer cell-derived exosomes, which contain proteins and RNAs, was much higher than that of normal cell-derived exosomes. Moreover, next-generation sequencing technology confirmed the presence of small non-coding RNAs in exosomes. Based on publicly available databases, we classified small non-coding RNAs. According to the microRNA profiles of exosomes, hsa-miR-21-5p and hsa-miR-30a-5p were two of the most abundant sequences among all libraries. The expression levels of the two microRNAs, miR-100 and miR-148a, in exosomes were validated through reverse transcription polymerase chain reaction. The reverse transcription polymerase chain reaction result, consistent with the trend of sequencing result, indicated a significant difference in exosomes between gastric cancer and gastric mucosal epithelial cell lines. We also predicted novel microRNA candidates but they need to be validated. This research provided an atlas of small noncoding RNA in exosomes and may make a little contribution to the understanding of exosomal RNA composition and finding parts of differential expression of RNAs in exosomes.

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“…46 Finally, numerous studies have revealed that some proteins within the exosomes are dependent on the cell type secreting them while others are independent from the parental cell. 47 These different types of proteins become incorporated into exosomes during exosome formation and serve as cargo for cellcell communication. Besides, protein exosomes are enriched in lipids such as saturated phospholipids (i.e., phosphatidyl-ethanolamin, phosphatidyL-serin, phosphatidyl-choline), sphingolipids (e.g.…”

Section: Compositionmentioning

confidence: 99%

Exosomes in cancer theranostic: Diamonds in the rough

Cordonnier

Chanteloup

Isambert

et al. 2017

Cell Adhesion & Migration

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During the last 10 years, exosomes, which are small vesicles of 50-200 nm diameter of endosomal origin, have aroused a great interest in the scientific and clinical community for their roles in intercellular communication in almost all physiological and pathological processes. Most cells can potentially release these nanovesicles that share with the parent cell a similar lipid bilayer with transmembrane proteins and a panel of enclosed soluble proteins such as heat shock proteins and genetic material, thus acting as potential nanoshuttles of biomarkers. Exosomes surface proteins allow their targeting and capture by recipient cells, while the exosomes' content can modify the physiological state of recipient cells. Tumor derived exosomes by interacting with other cells of the tumor microenvironment modulate tumor progression, angiogenic switch, metastasis, and immune escape. Targeting tumor-derived exosomes might be an interesting approach in cancer therapy. Furthermore, because a key issue to improve cancer patients' outcome relies on earlier cancer diagnosis (metastases, as opposed to the primary tumor, are responsible for most cancer deaths) exosomes have been put forward as promising biomarker candidates for cancer diagnosis and prognosis. This review summarizes the roles of exosomes in cancer and clinical interest, focusing on the importance of exosomal heat shock proteins (HSP). The challenges of clinical translation of HSPexosomes as therapeutic targets and biomarkers for early cancer detection are also discussed.

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Exosomes as Biomarker Enriched Microvesicles: Characterization of Exosomal Proteins Derived from a Panel of Prostate Cell Lines with Distinct AR Phenotypes

Cited by 195 publications

References 93 publications

Exosomes bind to autotaxin and act as a physiological delivery mechanism to stimulate LPA receptor signalling in cells

Exosomes bind to autotaxin and act as a physiological delivery mechanism to stimulate LPA receptor signalling in cells

Characterization of exosomal RNAs derived from human gastric cancer cells by deep sequencing

Exosomes in cancer theranostic: Diamonds in the rough

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