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| Status |
Public on Aug 31, 2015 |
| Title |
CLL exosomes modulate the transcriptome and behaviour of recipient stromal cells and are selectively enriched in miR-202-3p [mirBase 13] |
| Platform organisms |
Homo sapiens; Human alphaherpesvirus 1; Human alphaherpesvirus 2; Macacine alphaherpesvirus 1; Human betaherpesvirus 5; human gammaherpesvirus 4; Herpesvirus saimiri (strain 11); JC polyomavirus; Human immunodeficiency virus 1; Human betaherpesvirus 6B; Human gammaherpesvirus 8; Merkel cell polyomavirus; Betapolyomavirus hominis; Betapolyomavirus macacae |
| Sample organism |
Homo sapiens |
| Experiment type |
Non-coding RNA profiling by array
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| Summary |
Bi-directional communication with the microenvironment is essential for homing and survival of cancer cells with implications for disease biology and behaviour. In chronic lymphocytic leukemia (CLL) the role of the microenvironment on malignant cell behaviour is well described. However, how CLL cells engage and recruit nurturing cells is poorly characterised. Here we demonstrate that CLL cells secrete exosomes that are nanovesicles originating from the fusion of multivesicular bodies with the plasma membrane, to shuttle proteins, lipids, microRNAs (miR) and mRNAs to recipient cells. We characterise and confirm the size (50 - 100 nm) and identity of the CLL-derived exosomes by Electron microscopy (EM), Atomic force microscopy (AFM), flow cytometry and western blotting using both exosomes-specific and CLL-specific markers. Incubation of CLL-exosomes, derived either from cell culture supernatants or from patient plasma, with human stromal cells shows that they are readily taken up into endosomes, and induce expression of genes such as c-fos and ATM as well as enhance proliferation of recipient HS-5 cells. Furthermore, we show that CLL exosomes encapsulate abundant small RNAs and are enriched in certain miRs and specifically hsa-miR-202-3p. We suggest that such specific packaging of miR-202-3p impacts on the expression of 'suppressor of fused' (Sufu), a Hedgehog (Hh) signalling intermediate, in the parental CLL cells. Thus, our data show that CLL cells secrete exosomes that alter the transcriptome and behaviour of recipient cells. Such communication with microenvironment is likely to have an important role in CLL disease biology.
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| Overall design |
miR analysis was carried out on 3 exosomal samples and 3 corresponding cellular samples from CLL patients. Exosomes are a discrete population of small (50-100 nm diameter) EVs of endosomal origin with a lipid membrane bilayer and a cup-shaped morphology. We used common reference design which allows visualization of variations between the samples. Each sample equals one array and each sample compared with common reference (Pool). The pool or common reference was a collection of 23 RNA samples isolated from 23 CLL cases. We hypothesised that CLL derived exosomes should contain unique miRs that are reflective of CLL cell content and additionally relevant for disease biology.
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| Contributor(s) |
Farahani M, Rubbi C, Liu L, Slupsky JR, Kalakonda N |
| Citation missing |
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| Submission date |
Jul 16, 2015 |
| Last update date |
Sep 01, 2015 |
| Contact name |
Mosavar Farahani |
| E-mail(s) |
mosavar@liv.ac.uk
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| Phone |
+44 151 7064144
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| Organization name |
University of Liverpool
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| Department |
Molecular and Clinical Cancer Medicine
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| Lab |
Haematology
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| Street address |
Daulby Street
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| City |
Liverpool |
| ZIP/Postal code |
L69 3GA |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL20657 |
miRCURY LNA microRNA Array, v.11.0 - hsa, mmu & rno, miRBase 13.0 |
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| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE70996 |
CLL exosomes modulate the transcriptome and behaviour of recipient stromal cells and are selectively enriched in miR-202-3p |
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| Relations |
| BioProject |
PRJNA290131 |
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