PMID- 27196940
OWN - NLM
STAT- MEDLINE
DCOM- 20170711
LR  - 20181202
IS  - 1582-4934 (Electronic)
IS  - 1582-1838 (Print)
IS  - 1582-1838 (Linking)
VI  - 20
IP  - 10
DP  - 2016 Oct
TI  - Chronic myelogenous leukaemia exosomes modulate bone marrow microenvironment 
      through activation of epidermal growth factor receptor.
PG  - 1829-39
LID - 10.1111/jcmm.12873 [doi]
AB  - Chronic myelogenous leukaemia (CML) is a clonal myeloproliferative disorder. 
      Recent evidence indicates that altered crosstalk between CML and mesenchymal 
      stromal cells may affect leukaemia survival; moreover, vesicles released by both 
      tumour and non-tumour cells into the microenvironment provide a suitable niche 
      for cancer cell growth and survival. We previously demonstrated that leukaemic 
      and stromal cells establish an exosome-mediated bidirectional crosstalk leading 
      to the production of IL8 in stromal cells, thus sustaining the survival of CML 
      cells. Human cell lines used are LAMA84 (CML cells), HS5 (stromal cells) and bone 
      marrow primary stromal cells; gene expression and protein analysis were performed 
      by real-time PCR and Western blot. IL8 and MMP9 secretions were evaluated by 
      ELISA. Exosomes were isolated from CML cells and blood samples of CML patients. 
      Here, we show that LAMA84 and CML patients' exosomes contain amphiregulin (AREG), 
      thus activating epidermal growth factor receptor (EGFR) signalling in stromal 
      cells. EGFR signalling increases the expression of SNAIL and its targets, MMP9 
      and IL8. We also demonstrated that pre-treatment of HS5 with LAMA84 exosomes 
      increases the expression of annexin A2 that promotes the adhesion of leukaemic 
      cells to the stromal monolayer, finally supporting the growth and invasiveness of 
      leukaemic cells. Leukaemic and stromal cells establish a bidirectional crosstalk: 
      exosomes promote proliferation and survival of leukaemic cells, both in vitro and 
      in vivo, by inducing IL8 secretion from stromal cells. We propose that this 
      mechanism is activated by a ligand-receptor interaction between AREG, found in 
      CML exosomes, and EGFR in bone marrow stromal cells.
CI  - (c) 2016 The Authors. Journal of Cellular and Molecular Medicine published by John 
      Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.
FAU - Corrado, Chiara
AU  - Corrado C
AD  - Dipartimento di Biopatologia e Biotecnologie Mediche, Universita degli studi di 
      Palermo, sezione di Biologia e Genetica, Palermo, Italy.
FAU - Saieva, Laura
AU  - Saieva L
AD  - Dipartimento di Biopatologia e Biotecnologie Mediche, Universita degli studi di 
      Palermo, sezione di Biologia e Genetica, Palermo, Italy.
FAU - Raimondo, Stefania
AU  - Raimondo S
AD  - Dipartimento di Biopatologia e Biotecnologie Mediche, Universita degli studi di 
      Palermo, sezione di Biologia e Genetica, Palermo, Italy.
FAU - Santoro, Alessandra
AU  - Santoro A
AD  - Divisione di Ematologia, A.O. Ospedali Riuniti Villa Sofia-Cervello, Palermo, 
      Italy.
FAU - De Leo, Giacomo
AU  - De Leo G
AD  - Dipartimento di Biopatologia e Biotecnologie Mediche, Universita degli studi di 
      Palermo, sezione di Biologia e Genetica, Palermo, Italy.
FAU - Alessandro, Riccardo
AU  - Alessandro R
AUID- ORCID: 0000-0002-9935-1040
AD  - Dipartimento di Biopatologia e Biotecnologie Mediche, Universita degli studi di 
      Palermo, sezione di Biologia e Genetica, Palermo, Italy. 
      riccardo.alessandro@unipa.it.
LA  - eng
PT  - Journal Article
DEP - 20160514
PL  - England
TA  - J Cell Mol Med
JT  - Journal of cellular and molecular medicine
JID - 101083777
RN  - 0 (Amphiregulin)
RN  - 0 (Annexin A2)
RN  - 0 (Interleukin-8)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Snail Family Transcription Factors)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
SB  - IM
MH  - Amphiregulin/metabolism
MH  - Annexin A2/metabolism
MH  - Bone Marrow Cells/*metabolism/*pathology
MH  - Cell Adhesion
MH  - Cell Line, Tumor
MH  - *Cellular Microenvironment
MH  - ErbB Receptors/*metabolism
MH  - Exosomes/*metabolism
MH  - Humans
MH  - Interleukin-8/metabolism
MH  - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/*metabolism/*pathology
MH  - Matrix Metalloproteinase 9/genetics/metabolism
MH  - Phosphorylation
MH  - RNA, Messenger/genetics/metabolism
MH  - RNA, Small Interfering/metabolism
MH  - Snail Family Transcription Factors/genetics/metabolism
MH  - Stromal Cells/metabolism
PMC - PMC4876029
OTO - NOTNLM
OT  - SNAIL
OT  - chronic myeloid leukaemia
OT  - epidermal growth factor receptor
OT  - exosomes
OT  - interleukin 8
EDAT- 2016/05/20 06:00
MHDA- 2017/07/14 06:00
PMCR- 2016/10/01
CRDT- 2016/05/20 06:00
PHST- 2015/11/24 00:00 [received]
PHST- 2016/03/08 00:00 [accepted]
PHST- 2016/05/20 06:00 [entrez]
PHST- 2016/05/20 06:00 [pubmed]
PHST- 2017/07/14 06:00 [medline]
PHST- 2016/10/01 00:00 [pmc-release]
AID - JCMM12873 [pii]
AID - 10.1111/jcmm.12873 [doi]
PST - ppublish
SO  - J Cell Mol Med. 2016 Oct;20(10):1829-39. doi: 10.1111/jcmm.12873. Epub 2016 May 
      14.