liu.seSearch for publications in DiVA
Change search
Link to record
Permanent link

Direct link
BETA
Välilä, Johanna
Publications (2 of 2) Show all publications
Tjomsland, V., Spångeus, A., Välilä, J., Sandström, P., Borch, K., Druid, H., . . . Larsson, M. (2011). Interleukin 1α sustains the expression of inflammatory factors in human pancreatic cancer microenvironment by targeting cancer-associated fibroblasts. Neoplasia, 13(8), 664-675
Open this publication in new window or tab >>Interleukin 1α sustains the expression of inflammatory factors in human pancreatic cancer microenvironment by targeting cancer-associated fibroblasts
Show others...
2011 (English)In: Neoplasia, ISSN 1522-8002, E-ISSN 1476-5586, Vol. 13, no 8, p. 664-675Article in journal (Refereed) Published
Abstract [en]

The tumor microenvironment in pancreatic ductal adenocarcinoma (PDAC) is dynamic with an extensive interaction between the stroma and tumor cells. The aim for this study was to delineate the cross-talk between PDAC and cancer-associated fibroblasts (CAFs) with focus on the mechanism creating the chronic inflammatory tumor milieu. We assessed the effects of the cross-talk between primary PDAC and CAF cell lines on the creation and sustenance of the inflammatory tumor microenvironment in pancreatic cancer. The coculture of primary PDAC and CAF cell lines enhanced the levels of inflammatory factors including IL-1á, IL-6, CXCL8, VEGFA, CCL20, and COX-2. CAFs were superior to tumor cells regarding the production of most inflammatory factors and tumor cell associated IL-1á was established as the initiator of the enhanced production of inflammatory factors through the binding of IL-1á to the active IL-1 receptor (IL-1R1) expressed predominantly by CAFs. Furthermore, we found a positive correlation between IL-1á and CXCL8 expression levels in PDAC tissues and correlation between IL-1á expression and the clinical outcome of the patients. This confirmed an important role for the IL-1 signaling cascade in the creation and sustenance of a tumor favorable microenvironment. Neutralization of the IL-1á signaling efficiently diminished the cross-talk induced production of inflammatory factors. These data suggest that the cross-talk between PDAC cells and the main stroma cell type, i.e. CAFs, is one essential factor in the formation of the inflammatory tumor environment and we propose that neutralization of the IL-1á signaling might be a potential therapy for this cancer.

Place, publisher, year, edition, pages
Neoplasia Press, 2011
Keywords
Pancreatic cancer, IL-1alpha, cancer associated fibroblasts, cross-talk
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:liu:diva-69954 (URN)10.1593/neo.11332 (DOI)000295942500001 ()21847358 (PubMedID)
Available from: 2011-08-09 Created: 2011-08-09 Last updated: 2017-12-08
Tjomsland, V., Spångeus, A., Välilä, J., Sandström, P., Borch, K., Druid, H., . . . Larsson, M. (2010). IL-1α Sustains the Inflammation in Human Pancreatic Cancer Microenvironment by Targeting Cancer Associated Fibroblasts. , 10(87)
Open this publication in new window or tab >>IL-1α Sustains the Inflammation in Human Pancreatic Cancer Microenvironment by Targeting Cancer Associated Fibroblasts
Show others...
2010 (English)Manuscript (preprint) (Other academic)
Abstract [en]

The tumor microenvironment in pancreatic ductal adenocarcinoma (PDAC) is dynamic with an extensive interaction between the stroma and tumor cells. Our aim for this study was to delineate the cross-talk between PDAC and cancer-associated fibroblasts (CAFs) with focus on the mechanism creating the chronic inflammatory tumor milieu. We assessed the effect cross talk between primary PDAC and CAF cell lines propagated from tumors had on the creation and sustenance of an inflammatory environment and what factors that were involved in establishing the inflammation.

The coculture of PDAC and CAF cell lines, propagated from tumor tissues, enhanced the levels of inflammatory factors including IL-1α, IL-6, CXCL8, VEGFA, CCL20, and COX-2. The production of these factors correlated with the expression detected in vivo in PDAC tissues. The key producers of nearly all inflammatory factors were the CAFs and not the tumor cells.

IL-1α was produced by the tumor cell lines, whereas almost all IL-1RI was expressed by CAFs thus corresponding to their in vivo expression profile in PDAC tissues, indicating a role for the IL-1 signaling cascade in a tumor favorable microenvironment. Neutralization of the IL-1α pathway efficiently diminished the cross talk induced production of inflammatory factors, both in stroma and tumor cells. These data suggest that the cross-talk between PDAC cells and the main stroma cell type, i.e. CAFs, is one contributing factor in the formation of the inflammatory tumor environment and we propose that the neutralization of IL-1α pathway might be a potential therapy for this cancer.

Keywords
Tumor stroma cross talk; pancreatic cancer; cancer associated fibroblasts; inflammation; IL-1α
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-67750 (URN)
Available from: 2011-04-26 Created: 2011-04-26 Last updated: 2011-04-26Bibliographically approved
Organisations

Search in DiVA

Show all publications