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IL-1α Sustains the ...
IL-1α Sustains the Inflammation in Human Pancreatic Cancer Microenvironment by Targeting Cancer Associated Fibroblasts
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- Tjomsland, Vegard (författare)
- Linköpings universitet,Molekylär virologi,Hälsouniversitetet
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- Spångeus, Anna (författare)
- Linköpings universitet,Internmedicin,Hälsouniversitetet
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- Välilä, Johanna (författare)
- Linköpings universitet,Molekylär virologi,Hälsouniversitetet
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visa fler...
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- Sandström, Per (författare)
- Östergötlands Läns Landsting,Linköpings universitet,Kirurgi,Hälsouniversitetet,Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala
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- Borch, Kurt (författare)
- Östergötlands Läns Landsting,Linköpings universitet,Kirurgi,Hälsouniversitetet,Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala
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- Druid, Henrik (författare)
- Department of Oncology-pathology, Karolinska Institutet, Stockholm, Sweden
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- Falkmer, Sture (författare)
- Department of Clinical Pathology, County Hospital Ryhov, Jönköping, Sweden
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- Falkmer, Ursula (författare)
- Department of Oncology, County Hospital Ryhov, Jönköping, Sweden
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- Messmer, Davorka (författare)
- Cancer Center, University of California San Diego, La Jolla, USA
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- Larsson, Marie (författare)
- Linköpings universitet,Molekylär virologi,Hälsouniversitetet
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(creator_code:org_t)
- 2010
- Engelska.
- Relaterad länk:
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https://urn.kb.se/re...
Abstract
Ämnesord
Stäng
- 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.
Nyckelord
- Tumor stroma cross talk; pancreatic cancer; cancer associated fibroblasts; inflammation; IL-1α
- MEDICINE
- MEDICIN
Publikations- och innehållstyp
- vet (ämneskategori)
- ovr (ämneskategori)
- Av författaren/redakt...
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Tjomsland, Vegar ...
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Spångeus, Anna
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Välilä, Johanna
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Sandström, Per
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Borch, Kurt
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Druid, Henrik
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visa fler...
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Falkmer, Sture
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Falkmer, Ursula
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Messmer, Davorka
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Larsson, Marie
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visa färre...
- Av lärosätet
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Linköpings universitet