Tumour cell-derived extracellular vesicles interact with mesenchymal stem cells to modulate the microenvironment and enhance cholangiocarcinoma growth

Hiroaki Haga, Irene K. Yan, Kenji Takahashi, Joseph Wood, Abba Zubair, Tushar C Patel

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1-13
Number of pages13
JournalJournal of Extracellular Vesicles
Volume4
Issue number2015
DOIs
StatePublished - 2015

Fingerprint

Cholangiocarcinoma
Mesenchymal Stromal Cells
Growth
Neoplasms
Extracellular Vesicles
Interleukin-6
Messenger RNA
Conditioned Culture Medium
Smooth Muscle
Actins
Bone Marrow
Phosphorylation
Cell Proliferation

Keywords

  • Biliary tract cancer
  • Exosomes
  • Gene expression
  • Paracrine signalling
  • RNA genes
  • Stem cells

ASJC Scopus subject areas

  • Cell Biology
  • Histology

Cite this

Tumour cell-derived extracellular vesicles interact with mesenchymal stem cells to modulate the microenvironment and enhance cholangiocarcinoma growth. / Haga, Hiroaki; Yan, Irene K.; Takahashi, Kenji; Wood, Joseph; Zubair, Abba; Patel, Tushar C.

In: Journal of Extracellular Vesicles, Vol. 4, No. 2015, 2015, p. 1-13.

Research output: Contribution to journalArticle

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AU - Zubair, Abba

AU - Patel, Tushar C

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