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Series GSE70995 Query DataSets for GSE70995
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 15]
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
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.
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.
Contributor(s) Farahani M, Rubbi C, Liu L, Slupsky JR, Kalakonda N
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Submission date Jul 16, 2015
Last update date Sep 01, 2015
Contact name Mosavar Farahani
Phone +44 151 7064144
Organization name University of Liverpool
Department Molecular and Clinical Cancer Medicine
Lab Haematology
Street address Daulby Street
City Liverpool
ZIP/Postal code L69 3GA
Country United Kingdom
Platforms (1)
GPL20658 miRCURY LNA microRNA Array, 5th generation - hsa, mmu & rno, miRBase 15.0
Samples (6)
GSM1824825 CLL Cellular RNA 4
GSM1824826 CLL Exosomal RNA 4
GSM1824827 CLL Cellular RNA 5
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
BioProject PRJNA290130

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE70995_LME_background-subtracted_Hy3.txt.gz 22.4 Kb (ftp)(http) TXT
GSE70995_RAW.tar 9.9 Mb (http)(custom) TAR (of TXT)
Processed data are available on Series record

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