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- Collection:
- Clark Atlanta University Faculty Publications
- Title:
- Ym1+ Macrophages Orchestrate Fibrosis, Lesion Growth, and Progression During Development of Murine Pancreatic Cancer
- Creator:
- Geou-Yarh Liou, Clark Atlanta University
- Date of Original:
- 2022-05
- Subject:
- Degrees, Academic
Dissertations, Academic - Location:
- United States, Georgia, Fulton County, Atlanta, 33.749, -84.38798
- Medium:
- articles
- Type:
- Text
- Format:
- application/pdf
- Description:
- Desmoplasia around pancreatic lesions is a barrier for immune cells and a hallmark of developing and established pancreatic cancer. However, the contribution of the innate immune system to this process is ill-defined. Using the KC mouse model and primary cells in vitro, we show that alternatively activated macrophages (AAM) crosstalk with pancreatic lesion cells and pancreatic stellate cells (PSCs) to mediate fibrosis and progression of lesions. TGFb1 secreted by AAM not only drives activation of quiescent PSCs but also in activated PSCs upregulates expression of TIMP1, a factor previously shown as crucial in fibrosis. Once activated, PSCs auto-stimulate proliferation via CXCL12. Furthermore, we found that TIMP1/CD63 signaling mediates PanIN lesion growth and TGFb1 contributes to a cadherin switch and drives structural collapse of lesions, indicating a potential progression step. Taken together, our data indicate TGFb1 produced by Ym1+ AAM as a major driver of processes that initiate the development of pancreatic cancer.
- Metadata URL:
- http://hdl.handle.net/20.500.12322/cau.ir:2022_liou_geou_yarh_1
- IIIF manifest:
- []
- Original Collection:
- iScience
- Holding Institution:
- Atlanta University Center Robert W. Woodruff Library
- Rights: