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Differential Contribution of Pancreatic Fibroblast Subsets to the Pancreatic Cancer Stroma
BACKGROUND & AIMS: Although the healthy pancreas consists mostly of epithelial cells, pancreatic cancer and the precursor lesions known as pancreatic intraepithelial neoplasia, are characterized by an extensive accumulation of fibroinflammatory stroma that includes a substantial and heterogeneou...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7399194/ https://www.ncbi.nlm.nih.gov/pubmed/32454112 http://dx.doi.org/10.1016/j.jcmgh.2020.05.004 |
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author | Garcia, Paloma E. Adoumie, Maeva Kim, Esther C. Zhang, Yaqing Scales, Michael K. El-Tawil, Yara S. Shaikh, Amara Z. Wen, Hui-Ju Bednar, Filip Allen, Ben L. Wellik, Deneen M. Crawford, Howard C. Pasca di Magliano, Marina |
author_facet | Garcia, Paloma E. Adoumie, Maeva Kim, Esther C. Zhang, Yaqing Scales, Michael K. El-Tawil, Yara S. Shaikh, Amara Z. Wen, Hui-Ju Bednar, Filip Allen, Ben L. Wellik, Deneen M. Crawford, Howard C. Pasca di Magliano, Marina |
author_sort | Garcia, Paloma E. |
collection | PubMed |
description | BACKGROUND & AIMS: Although the healthy pancreas consists mostly of epithelial cells, pancreatic cancer and the precursor lesions known as pancreatic intraepithelial neoplasia, are characterized by an extensive accumulation of fibroinflammatory stroma that includes a substantial and heterogeneous fibroblast population. The cellular origin of fibroblasts within the stroma has not been determined. Here, we show that the Gli1 and Hoxb6 markers label distinct fibroblast populations in the healthy mouse pancreas. We then set out to determine whether these distinct fibroblast populations expanded during carcinogenesis. METHODS: We developed genetically engineered models using a dual-recombinase approach that allowed us to induce pancreatic cancer formation through codon-optimized Flp recombinase-driven epithelial recombination of Kirsten rat sarcoma viral oncogene homolog while labeling Gli1(+) or Hoxb6(+) fibroblasts in an inducible manner. By using these models, we lineage-traced these 2 fibroblast populations during the process of carcinogenesis. RESULTS: Although in the healthy pancreas Gli1(+) fibroblasts and Hoxb6(+) fibroblasts are present in similar numbers, they contribute differently to the stroma in carcinogenesis. Namely, Gli1(+) fibroblasts expand dramatically, whereas Hoxb6(+) cells do not. CONCLUSIONS: Fibroblasts present in the healthy pancreas expand during carcinogenesis, but with a different prevalence for different subtypes. Here, we compared Gli1(+) and Hoxb6(+) fibroblasts and found only Gli1(+) expanded to contribute to the stroma during pancreatic carcinogenesis. |
format | Online Article Text |
id | pubmed-7399194 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-73991942020-08-06 Differential Contribution of Pancreatic Fibroblast Subsets to the Pancreatic Cancer Stroma Garcia, Paloma E. Adoumie, Maeva Kim, Esther C. Zhang, Yaqing Scales, Michael K. El-Tawil, Yara S. Shaikh, Amara Z. Wen, Hui-Ju Bednar, Filip Allen, Ben L. Wellik, Deneen M. Crawford, Howard C. Pasca di Magliano, Marina Cell Mol Gastroenterol Hepatol Original Research BACKGROUND & AIMS: Although the healthy pancreas consists mostly of epithelial cells, pancreatic cancer and the precursor lesions known as pancreatic intraepithelial neoplasia, are characterized by an extensive accumulation of fibroinflammatory stroma that includes a substantial and heterogeneous fibroblast population. The cellular origin of fibroblasts within the stroma has not been determined. Here, we show that the Gli1 and Hoxb6 markers label distinct fibroblast populations in the healthy mouse pancreas. We then set out to determine whether these distinct fibroblast populations expanded during carcinogenesis. METHODS: We developed genetically engineered models using a dual-recombinase approach that allowed us to induce pancreatic cancer formation through codon-optimized Flp recombinase-driven epithelial recombination of Kirsten rat sarcoma viral oncogene homolog while labeling Gli1(+) or Hoxb6(+) fibroblasts in an inducible manner. By using these models, we lineage-traced these 2 fibroblast populations during the process of carcinogenesis. RESULTS: Although in the healthy pancreas Gli1(+) fibroblasts and Hoxb6(+) fibroblasts are present in similar numbers, they contribute differently to the stroma in carcinogenesis. Namely, Gli1(+) fibroblasts expand dramatically, whereas Hoxb6(+) cells do not. CONCLUSIONS: Fibroblasts present in the healthy pancreas expand during carcinogenesis, but with a different prevalence for different subtypes. Here, we compared Gli1(+) and Hoxb6(+) fibroblasts and found only Gli1(+) expanded to contribute to the stroma during pancreatic carcinogenesis. Elsevier 2020-05-23 /pmc/articles/PMC7399194/ /pubmed/32454112 http://dx.doi.org/10.1016/j.jcmgh.2020.05.004 Text en © 2020 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original Research Garcia, Paloma E. Adoumie, Maeva Kim, Esther C. Zhang, Yaqing Scales, Michael K. El-Tawil, Yara S. Shaikh, Amara Z. Wen, Hui-Ju Bednar, Filip Allen, Ben L. Wellik, Deneen M. Crawford, Howard C. Pasca di Magliano, Marina Differential Contribution of Pancreatic Fibroblast Subsets to the Pancreatic Cancer Stroma |
title | Differential Contribution of Pancreatic Fibroblast Subsets to the Pancreatic Cancer Stroma |
title_full | Differential Contribution of Pancreatic Fibroblast Subsets to the Pancreatic Cancer Stroma |
title_fullStr | Differential Contribution of Pancreatic Fibroblast Subsets to the Pancreatic Cancer Stroma |
title_full_unstemmed | Differential Contribution of Pancreatic Fibroblast Subsets to the Pancreatic Cancer Stroma |
title_short | Differential Contribution of Pancreatic Fibroblast Subsets to the Pancreatic Cancer Stroma |
title_sort | differential contribution of pancreatic fibroblast subsets to the pancreatic cancer stroma |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7399194/ https://www.ncbi.nlm.nih.gov/pubmed/32454112 http://dx.doi.org/10.1016/j.jcmgh.2020.05.004 |
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