Impact by pancreatic stellate cells on epithelial-mesenchymal transition and pancreatic cancer cell invasion : Adding a third dimension in vitro
(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.
(Less)
- author
- Karnevi, Emelie LU ; Rosendahl, Ann H. LU ; Hilmersson, Katarzyna Said LU ; Saleem, Moin A. and Andersson, Roland LU
- organization
- publishing date
- 2016-08-15
- 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
- pmid:27443257
- 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
- 2024-10-05 09:13:56
@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}}, keywords = {{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}}, doi = {{10.1016/j.yexcr.2016.07.017}}, volume = {{346}}, year = {{2016}}, }