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Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer
Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery. Cold Spring Harbor Laboratory and Lustgarten Foundation Pancreatic Cancer Research Laboratory, Cold Spring Harbor, NY 11724.ORCID iD: 0000-0002-5847-2778
2017 (English)In: Journal of Experimental Medicine, ISSN 0022-1007, E-ISSN 1540-9538, Vol. 214, no 3, 579-596 p.Article in journal (Refereed) Published
Abstract [en]

Pancreatic stellate cells (PSCs) differentiate into cancer-associated fibroblasts (CAFs) that produce desmoplastic stroma, thereby modulating disease progression and therapeutic response in pancreatic ductal adenocarcinoma (PDA). However, it is unknown whether CAFs uniformly carry out these tasks or if subtypes of CAFs with distinct phenotypes in PDA exist. We identified a CAF subpopulation with elevated expression of a-smooth muscle actin (alpha SMA) located immediately adjacent to neoplastic cells in mouse and human PDA tissue. We recapitulated this finding in co-cultures of murine PSCs and PDA organoids, and demonstrated that organoid-activated CAFs produced desmoplastic stroma. The co-cultures showed cooperative interactions and revealed another distinct subpopulation of CAFs, located more distantly from neoplastic cells, which lacked elevated aSMA expression and instead secreted IL6 and additional inflammatory mediators. These findings were corroborated in mouse and human PDA tissue, providing direct evidence for CAF heterogeneity in PDA tumor biology with implications for disease etiology and therapeutic development.

Place, publisher, year, edition, pages
2017. Vol. 214, no 3, 579-596 p.
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:umu:diva-132073DOI: 10.1084/jem.20162024ISI: 000395828600002PubMedID: 28232471OAI: oai:DiVA.org:umu-132073DiVA: diva2:1078039
Available from: 2017-03-02 Created: 2017-03-02 Last updated: 2017-05-05Bibliographically approved

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CiteExportLink to record
Permanent link

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Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
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  • asciidoc
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