Epithelial-Myeloid cell crosstalk regulates acinar cell plasticity and pancreatic remodeling in mice
Dedifferentiation of acini to duct-like cells occurs during the physiologic damage response in the pancreas, but this process can be co-opted by oncogenic Kras to drive carcinogenesis. Myeloid cells infiltrate the pancreas during the onset of pancreatic cancer, and promote carcinogenesis. Here, we s...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2017-10-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/27388 |
| _version_ | 1811253350222528512 |
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| author | Yaqing Zhang Wei Yan Esha Mathew Kevin T Kane Arthur Brannon III Maeva Adoumie Alekya Vinta Howard C Crawford Marina Pasca di Magliano |
| author_facet | Yaqing Zhang Wei Yan Esha Mathew Kevin T Kane Arthur Brannon III Maeva Adoumie Alekya Vinta Howard C Crawford Marina Pasca di Magliano |
| author_sort | Yaqing Zhang |
| collection | DOAJ |
| description | Dedifferentiation of acini to duct-like cells occurs during the physiologic damage response in the pancreas, but this process can be co-opted by oncogenic Kras to drive carcinogenesis. Myeloid cells infiltrate the pancreas during the onset of pancreatic cancer, and promote carcinogenesis. Here, we show that the function of infiltrating myeloid cells is regulated by oncogenic Kras expressed in epithelial cells. In the presence of oncogenic Kras, myeloid cells promote acinar dedifferentiation and carcinogenesis. Upon inactivation of oncogenic Kras, myeloid cells promote re-differentiation of acinar cells, remodeling of the fibrotic stroma and tissue repair. Intriguingly, both aspects of myeloid cell activity depend, at least in part, on activation of EGFR/MAPK signaling, with different subsets of ligands and receptors in different target cells promoting carcinogenesis or repair, respectively. Thus, the cross-talk between epithelial cells and infiltrating myeloid cells determines the balance between tissue repair and carcinogenesis in the pancreas. |
| first_indexed | 2024-04-12T16:49:35Z |
| format | Article |
| id | doaj.art-18440f62d47549e7a0383006b185ab9a |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T16:49:35Z |
| publishDate | 2017-10-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-18440f62d47549e7a0383006b185ab9a2022-12-22T03:24:27ZengeLife Sciences Publications LtdeLife2050-084X2017-10-01610.7554/eLife.27388Epithelial-Myeloid cell crosstalk regulates acinar cell plasticity and pancreatic remodeling in miceYaqing Zhang0Wei Yan1Esha Mathew2Kevin T Kane3Arthur Brannon III4Maeva Adoumie5Alekya Vinta6Howard C Crawford7Marina Pasca di Magliano8https://orcid.org/0000-0001-9632-9035Department of Surgery, University of Michigan, Ann Arbor, United StatesDepartment of Surgery, University of Michigan, Ann Arbor, United States; Department of Pathology, Xijing Hospital, Fourth Military Medical University, Xi’an, ChinaProgram in Cellular and Molecular Biology, University of Michigan, Ann Arbor, United StatesDepartment of Surgery, University of Michigan, Ann Arbor, United StatesProgram in Cellular and Molecular Biology, University of Michigan, Ann Arbor, United States; Medical Scientist Training Program, University of Michigan, Ann Arbor, United StatesCollege of Literature, Science, and the Arts, University of Michigan, Ann Arbor, United StatesCollege of Literature, Science, and the Arts, University of Michigan, Ann Arbor, United StatesDepartment of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, United States; Department of Internal Medicine, University of Michigan, Ann Arbor, United States; Comprehensive Cancer Center, University of Michigan, Ann Arbor, United StatesDepartment of Surgery, University of Michigan, Ann Arbor, United States; Program in Cellular and Molecular Biology, University of Michigan, Ann Arbor, United States; Comprehensive Cancer Center, University of Michigan, Ann Arbor, United States; Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, United StatesDedifferentiation of acini to duct-like cells occurs during the physiologic damage response in the pancreas, but this process can be co-opted by oncogenic Kras to drive carcinogenesis. Myeloid cells infiltrate the pancreas during the onset of pancreatic cancer, and promote carcinogenesis. Here, we show that the function of infiltrating myeloid cells is regulated by oncogenic Kras expressed in epithelial cells. In the presence of oncogenic Kras, myeloid cells promote acinar dedifferentiation and carcinogenesis. Upon inactivation of oncogenic Kras, myeloid cells promote re-differentiation of acinar cells, remodeling of the fibrotic stroma and tissue repair. Intriguingly, both aspects of myeloid cell activity depend, at least in part, on activation of EGFR/MAPK signaling, with different subsets of ligands and receptors in different target cells promoting carcinogenesis or repair, respectively. Thus, the cross-talk between epithelial cells and infiltrating myeloid cells determines the balance between tissue repair and carcinogenesis in the pancreas.https://elifesciences.org/articles/27388pancreatic cancermyeloid celltissue remodelingsignaling pathwaysEGFMAPK |
| spellingShingle | Yaqing Zhang Wei Yan Esha Mathew Kevin T Kane Arthur Brannon III Maeva Adoumie Alekya Vinta Howard C Crawford Marina Pasca di Magliano Epithelial-Myeloid cell crosstalk regulates acinar cell plasticity and pancreatic remodeling in mice eLife pancreatic cancer myeloid cell tissue remodeling signaling pathways EGF MAPK |
| title | Epithelial-Myeloid cell crosstalk regulates acinar cell plasticity and pancreatic remodeling in mice |
| title_full | Epithelial-Myeloid cell crosstalk regulates acinar cell plasticity and pancreatic remodeling in mice |
| title_fullStr | Epithelial-Myeloid cell crosstalk regulates acinar cell plasticity and pancreatic remodeling in mice |
| title_full_unstemmed | Epithelial-Myeloid cell crosstalk regulates acinar cell plasticity and pancreatic remodeling in mice |
| title_short | Epithelial-Myeloid cell crosstalk regulates acinar cell plasticity and pancreatic remodeling in mice |
| title_sort | epithelial myeloid cell crosstalk regulates acinar cell plasticity and pancreatic remodeling in mice |
| topic | pancreatic cancer myeloid cell tissue remodeling signaling pathways EGF MAPK |
| url | https://elifesciences.org/articles/27388 |
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