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Impact by pancreatic stellate cells on epithelial-mesenchymal transition and pancreatic cancer cell invasion : Adding a third dimension in vitro

Karnevi, Emelie LU ; Rosendahl, Ann H. LU ; Hilmersson, Katarzyna Said LU ; Saleem, Moin A. and Andersson, Roland LU (2016) In Experimental Cell Research 346(2). p.206-215
Abstract

Pancreatic cancer is associated with a highly abundant stroma and low-grade inflammation. In the local tumour microenvironment, elevated glucose levels, the presence of tumour-associated stellate cells and macrophages are hypothesised to promote the tumour progression and invasion. The present study investigated the influence by the microenvironment on pancreatic cancer cell invasion in vitro. After co-culture with tumour-associated pancreatic stellate cells (TPSCs), pancreatic cancer cells displayed up to 8-fold reduction in levels of epithelial-mesenchymal transition (EMT) markers E-cadherin and ZO-1, while β-catenin and vimentin levels were increased. A 3D organotypic model showed that TPSCs stimulated pancreatic cancer cell... (More)

Pancreatic cancer is associated with a highly abundant stroma and low-grade inflammation. In the local tumour microenvironment, elevated glucose levels, the presence of tumour-associated stellate cells and macrophages are hypothesised to promote the tumour progression and invasion. The present study investigated the influence by the microenvironment on pancreatic cancer cell invasion in vitro. After co-culture with tumour-associated pancreatic stellate cells (TPSCs), pancreatic cancer cells displayed up to 8-fold reduction in levels of epithelial-mesenchymal transition (EMT) markers E-cadherin and ZO-1, while β-catenin and vimentin levels were increased. A 3D organotypic model showed that TPSCs stimulated pancreatic cancer cell invasion, both as single cell (PANC-1) and cohort (MIAPaCa-2) invasion. The combined presence of TPSCs and M2-like macrophages induced invasion of the non-invasive BxPC-3 cells. High glucose conditions further enhanced changes in EMT markers as well as the cancer cell invasion. In summary, co-culture with TPSCs induced molecular changes associated with EMT in pancreatic cancer cells, regardless of differentiation status, and the organotypic model demonstrated the influence of microenvironmental factors, such as glucose, stellate cells and macrophages, on pancreatic cancer cell invasion.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
3D organotypic model, Epithelial-mesenchymal transition, Invasion, Macrophages, Pancreatic cancer, Pancreatic stellate cells
in
Experimental Cell Research
volume
346
issue
2
pages
10 pages
publisher
Academic Press
external identifiers
  • scopus:84991256772
  • wos:000381777000007
ISSN
0014-4827
DOI
10.1016/j.yexcr.2016.07.017
language
English
LU publication?
yes
id
9ee4f44e-89f3-4a4d-8401-3ec1aa63ed90
date added to LUP
2016-12-29 13:22:19
date last changed
2017-09-18 11:34:15
@article{9ee4f44e-89f3-4a4d-8401-3ec1aa63ed90,
  abstract     = {<p>Pancreatic cancer is associated with a highly abundant stroma and low-grade inflammation. In the local tumour microenvironment, elevated glucose levels, the presence of tumour-associated stellate cells and macrophages are hypothesised to promote the tumour progression and invasion. The present study investigated the influence by the microenvironment on pancreatic cancer cell invasion in vitro. After co-culture with tumour-associated pancreatic stellate cells (TPSCs), pancreatic cancer cells displayed up to 8-fold reduction in levels of epithelial-mesenchymal transition (EMT) markers E-cadherin and ZO-1, while β-catenin and vimentin levels were increased. A 3D organotypic model showed that TPSCs stimulated pancreatic cancer cell invasion, both as single cell (PANC-1) and cohort (MIAPaCa-2) invasion. The combined presence of TPSCs and M2-like macrophages induced invasion of the non-invasive BxPC-3 cells. High glucose conditions further enhanced changes in EMT markers as well as the cancer cell invasion. In summary, co-culture with TPSCs induced molecular changes associated with EMT in pancreatic cancer cells, regardless of differentiation status, and the organotypic model demonstrated the influence of microenvironmental factors, such as glucose, stellate cells and macrophages, on pancreatic cancer cell invasion.</p>},
  author       = {Karnevi, Emelie and Rosendahl, Ann H. and Hilmersson, Katarzyna Said and Saleem, Moin A. and Andersson, Roland},
  issn         = {0014-4827},
  keyword      = {3D organotypic model,Epithelial-mesenchymal transition,Invasion,Macrophages,Pancreatic cancer,Pancreatic stellate cells},
  language     = {eng},
  month        = {08},
  number       = {2},
  pages        = {206--215},
  publisher    = {Academic Press},
  series       = {Experimental Cell Research},
  title        = {Impact by pancreatic stellate cells on epithelial-mesenchymal transition and pancreatic cancer cell invasion : Adding a third dimension in vitro},
  url          = {http://dx.doi.org/10.1016/j.yexcr.2016.07.017},
  volume       = {346},
  year         = {2016},
}