Tumour cell–derived extracellular vesicles interact with mesenchymal stem cells to modulate the microenvironment and enhance cholangiocarcinoma growth
The contributions of mesenchymal stem cells (MSCs) to tumour growth and stroma formation are poorly understood. Tumour cells can transfer genetic information and modulate cell signalling in other cells through the release of extracellular vesicles (EVs). We examined the contribution of EV-mediated i...
Main Authors: | , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Taylor & Francis Group
2015-01-01
|
Series: | Journal of Extracellular Vesicles |
Subjects: | |
Online Access: | http://www.journalofextracellularvesicles.net/index.php/jev/article/view/24900/pdf_4 |
id |
doaj-12b2f0ea90344e5db9dcc919b1b93796 |
---|---|
record_format |
Article |
spelling |
doaj-12b2f0ea90344e5db9dcc919b1b937962020-11-24T22:38:06ZengTaylor & Francis GroupJournal of Extracellular Vesicles2001-30782015-01-014011310.3402/jev.v4.2490024900Tumour cell–derived extracellular vesicles interact with mesenchymal stem cells to modulate the microenvironment and enhance cholangiocarcinoma growthHiroaki Haga0Irene K. Yan1Kenji Takahashi2Joseph Wood3Abba Zubair4Tushar Patel5 Department of Cancer Biology, Mayo Clinic Jacksonville, FL, USA Department of Cancer Biology, Mayo Clinic Jacksonville, FL, USA Department of Cancer Biology, Mayo Clinic Jacksonville, FL, USA Department of Cancer Biology, Mayo Clinic Jacksonville, FL, USA Department of Laboratory Medicine and Pathology, Mayo Clinic, Jacksonville, FL, USA Department of Cancer Biology, Mayo Clinic Jacksonville, FL, USAThe contributions of mesenchymal stem cells (MSCs) to tumour growth and stroma formation are poorly understood. Tumour cells can transfer genetic information and modulate cell signalling in other cells through the release of extracellular vesicles (EVs). We examined the contribution of EV-mediated inter-cellular signalling between bone marrow MSCs and tumour cells in human cholangiocarcinoma, highly desmoplastic cancers that are characterized by tumour cells closely intertwined within a dense fibrous stroma. Exposure of MSCs to tumour cell–derived EVs enhanced MSC migratory capability and expression of alpha-smooth muscle actin mRNA, in addition to mRNA expression and release of CXCL-1, CCL2 and IL-6. Conditioned media from MSCs exposed to tumour cell–derived EVs increased STAT-3 phosphorylation and proliferation in tumour cells. These effects were completely blocked by anti-IL-6R antibody. In conclusion, tumour cell–derived EVs can contribute to the generation of tumour stroma through fibroblastic differentiation of MSCs, and can also selectively modulate the cellular release of soluble factors such as IL-6 by MSCs that can, in turn, alter tumour cell proliferation. Thus, malignant cells can “educate” MSCs to induce local microenvironmental changes that enhance tumour cell growth.http://www.journalofextracellularvesicles.net/index.php/jev/article/view/24900/pdf_4biliary tract cancerstem cellsexosomesgene expressionRNA genesparacrine signalling |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Hiroaki Haga Irene K. Yan Kenji Takahashi Joseph Wood Abba Zubair Tushar Patel |
spellingShingle |
Hiroaki Haga Irene K. Yan Kenji Takahashi Joseph Wood Abba Zubair Tushar Patel Tumour cell–derived extracellular vesicles interact with mesenchymal stem cells to modulate the microenvironment and enhance cholangiocarcinoma growth Journal of Extracellular Vesicles biliary tract cancer stem cells exosomes gene expression RNA genes paracrine signalling |
author_facet |
Hiroaki Haga Irene K. Yan Kenji Takahashi Joseph Wood Abba Zubair Tushar Patel |
author_sort |
Hiroaki Haga |
title |
Tumour cell–derived extracellular vesicles interact with mesenchymal stem cells to modulate the microenvironment and enhance cholangiocarcinoma growth |
title_short |
Tumour cell–derived extracellular vesicles interact with mesenchymal stem cells to modulate the microenvironment and enhance cholangiocarcinoma growth |
title_full |
Tumour cell–derived extracellular vesicles interact with mesenchymal stem cells to modulate the microenvironment and enhance cholangiocarcinoma growth |
title_fullStr |
Tumour cell–derived extracellular vesicles interact with mesenchymal stem cells to modulate the microenvironment and enhance cholangiocarcinoma growth |
title_full_unstemmed |
Tumour cell–derived extracellular vesicles interact with mesenchymal stem cells to modulate the microenvironment and enhance cholangiocarcinoma growth |
title_sort |
tumour cell–derived extracellular vesicles interact with mesenchymal stem cells to modulate the microenvironment and enhance cholangiocarcinoma growth |
publisher |
Taylor & Francis Group |
series |
Journal of Extracellular Vesicles |
issn |
2001-3078 |
publishDate |
2015-01-01 |
description |
The contributions of mesenchymal stem cells (MSCs) to tumour growth and stroma formation are poorly understood. Tumour cells can transfer genetic information and modulate cell signalling in other cells through the release of extracellular vesicles (EVs). We examined the contribution of EV-mediated inter-cellular signalling between bone marrow MSCs and tumour cells in human cholangiocarcinoma, highly desmoplastic cancers that are characterized by tumour cells closely intertwined within a dense fibrous stroma. Exposure of MSCs to tumour cell–derived EVs enhanced MSC migratory capability and expression of alpha-smooth muscle actin mRNA, in addition to mRNA expression and release of CXCL-1, CCL2 and IL-6. Conditioned media from MSCs exposed to tumour cell–derived EVs increased STAT-3 phosphorylation and proliferation in tumour cells. These effects were completely blocked by anti-IL-6R antibody. In conclusion, tumour cell–derived EVs can contribute to the generation of tumour stroma through fibroblastic differentiation of MSCs, and can also selectively modulate the cellular release of soluble factors such as IL-6 by MSCs that can, in turn, alter tumour cell proliferation. Thus, malignant cells can “educate” MSCs to induce local microenvironmental changes that enhance tumour cell growth. |
topic |
biliary tract cancer stem cells exosomes gene expression RNA genes paracrine signalling |
url |
http://www.journalofextracellularvesicles.net/index.php/jev/article/view/24900/pdf_4 |
work_keys_str_mv |
AT hiroakihaga tumourcellderivedextracellularvesiclesinteractwithmesenchymalstemcellstomodulatethemicroenvironmentandenhancecholangiocarcinomagrowth AT irenekyan tumourcellderivedextracellularvesiclesinteractwithmesenchymalstemcellstomodulatethemicroenvironmentandenhancecholangiocarcinomagrowth AT kenjitakahashi tumourcellderivedextracellularvesiclesinteractwithmesenchymalstemcellstomodulatethemicroenvironmentandenhancecholangiocarcinomagrowth AT josephwood tumourcellderivedextracellularvesiclesinteractwithmesenchymalstemcellstomodulatethemicroenvironmentandenhancecholangiocarcinomagrowth AT abbazubair tumourcellderivedextracellularvesiclesinteractwithmesenchymalstemcellstomodulatethemicroenvironmentandenhancecholangiocarcinomagrowth AT tusharpatel tumourcellderivedextracellularvesiclesinteractwithmesenchymalstemcellstomodulatethemicroenvironmentandenhancecholangiocarcinomagrowth |
_version_ |
1725714588743237632 |