Somerville, T. D. D., Biffi, G., DaBler-Plenker, J., Hur, S.K., He, X.-Y., Vance, K.E., Miyabayashi, K., Xu, Y., Maia-Silva, D., Klingbeil, O., Demerdash, O. E., Preall, J. B., Hollingsworth, M. A., Egeblad, M., Tuveson, D. A., Vakoc, C. R.
(April 2020)
Squamous trans-differentiation of pancreatic cancer cells promotes stromal inflammation.
Elife, 9.
e53381.
ISSN 2050-084x
(Public Dataset)
Abstract
A highly aggressive subset of pancreatic ductal adenocarcinomas undergo trans-differentiation into the squamous lineage during disease progression. Here, we investigated whether squamous trans-differentiation of human and mouse pancreatic cancer cells can influence the phenotype of non-neoplastic cells in the tumor microenvironment. Conditioned media experiments revealed that squamous pancreatic cancer cells secrete factors that recruit neutrophils and convert pancreatic stellate cells into cancer-associated fibroblasts (CAFs) that express inflammatory cytokines at high levels. We use gain- and loss-of-function approaches to show that squamous-subtype pancreatic tumor models become enriched with neutrophils and inflammatory CAFs in a p63-dependent manner. These effects occur, at least in part, through p63-mediated activation of enhancers at pro-inflammatory cytokine loci, which includes IL1A and CXCL1 as key targets. Taken together, our findings reveal enhanced tissue inflammation as a consequence of squamous trans-differentiation in pancreatic cancer, thus highlighting an instructive role of tumor cell lineage in reprogramming the stromal microenvironment.
Item Type: |
Paper
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Subjects: |
diseases & disorders > cancer diseases & disorders diseases & disorders > neoplasms organism description > animal diseases & disorders > cancer > cancer-associated cell types diseases & disorders > cancer > cancer-associated cell types > cancer-associated fibroblast organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions diseases & disorders > inflammation > cytokines organs, tissues, organelles, cell types and functions > cell types and functions > cell types > fibroblasts organs, tissues, organelles, cell types and functions > cell types and functions > cell types > fibroblasts organs, tissues, organelles, cell types and functions > cell types and functions > cell types > fibroblasts diseases & disorders > inflammation organism description > animal > mammal organism description > animal > mammal > rodent > mouse organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neutrophils organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neutrophils organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neutrophils organs, tissues, organelles, cell types and functions diseases & disorders > cancer > cancer types > pancreatic cancer organism description > animal > mammal > rodent |
CSHL Authors: |
![](http://repository.cshl.edu/util/irpics/vakoc_christopher_r.jpg) Vakoc, Christopher R.![](http://repository.cshl.edu/util/irpics/tuveson_david_a.jpg) Tuveson, David A.![](http://repository.cshl.edu/util/irpics/egeblad_mikala.jpg) Egeblad, Mikala![](http://repository.cshl.edu/util/irpics/preall_jonathan.jpg) Preall, Jonathan![](http://repository.cshl.edu/util/irpics/somerville_timothy.jpg) Somerville, Timothy![](http://repository.cshl.edu/util/irpics/biffi_giulia.jpg) Biffi, Giulia![](http://repository.cshl.edu/util/irpics/dabler-plenker_juliane.jpg) DaBler-Plenker, Juliane![](http://repository.cshl.edu/util/irpics/he_xueyan.jpg) He, Xueyan![](http://repository.cshl.edu/util/irpics/miyabayashi_koji.jpg) Miyabayashi, Koji![](http://repository.cshl.edu/util/irpics/xu_yali.jpg) Xu, Yali![](http://repository.cshl.edu/util/irpics/maia_silva_diogo.jpg) Maia-Silva, Diogo![](http://repository.cshl.edu/util/irpics/klingbeil_olaf.jpg) Klingbeil, Olaf![](http://repository.cshl.edu/util/irpics/hur_stellak.jpg) Hur, Stella K.![](http://repository.cshl.edu/util/irpics/demerdash_osamae.jpg) Demerdash, Osama E.
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Communities: |
CSHL Cancer Center Program > Cancer Genetics and Genomics Program CSHL Cancer Center Program > Cellular Communication in Cancer Program CSHL Cancer Center Program > Gene Regulation and Inheritance Program CSHL Cancer Center Shared Resources > Animal Shared Resource CSHL labs > Egeblad lab CSHL labs > Preall lab CSHL labs > Tuveson lab CSHL labs > Vakoc lab School of Biological Sciences > Publications |
Depositing User: |
Adrian Gomez
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Date: |
24 April 2020 |
Date Deposited: |
07 May 2020 14:10 |
Last Modified: |
01 Feb 2024 18:42 |
PMCID: |
PMC7200154 |
Related URLs: |
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Dataset ID: |
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URI: |
https://repository.cshl.edu/id/eprint/39345 |
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