Type I collagen deletion in αSMA+ myofibroblasts augments immune suppression and accelerates progression of pancreatic cancer
Open accessAbstract
Stromal desmoplastic reaction in pancreatic ductal adenocarcinoma (PDAC) involves significant accumulation of type I collagen (Col1). However, the precise molecular and mechanistic contribution of Col1 in PDAC progression remains unknown. Activated pancreatic stellate cells/αSMA+ myofibroblasts are major contributors of Col1 in the PDAC stroma. We use a dual-recombinase genetic mouse model of spontaneous PDAC to delete Col1 specifically in myofibroblasts. This results in significant reduction of total stromal Col1 content and accelerates the emergence of PanINs and PDAC, decreasing overall survival. Col1 deletion leads to Cxcl5 upregulation in cancer cells via SOX9. Increase in Cxcl5 is associated with recruitment of myeloid-derived suppressor cells and suppression of CD8+ T cells, which can be attenuated with combined targeting of CXCR2 and CCR2 to restrain accelerated PDAC progression in the setting of stromal Col1 deletion. Our results unravel the fundamental role of myofibroblast-derived Co1l in regulating tumor immunity and restraining PDAC progression.
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The majority of collagen in PDAC is type I collagen, largely generated by CAFs.
“The majority of collagen is type I collagen164, largely generated by CAFs147,165”
From Pancreatic cancer: Advances and challenges (2023) · cites this paper as [165]
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Pancreatic cancer: Advances and challenges
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- Authors
- Chen, Y., Kim, J., Yang, S., Wang, H., Wu, C.-J., Sugimoto, H., LeBleu, V. S., & Kalluri, R.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- Corresponding author
- Kalluri, Raghu
- ORCID
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2021-04
- Volume
- 39
- Issue
- 4
- Pages
- 548-565.e6
- ISSN
- 1535-6108 (ISSN-L)
- PMC
- PMC8423173
- OpenAlex
- W3133734054
- Cited by
- 566
- References
- 100
- Citations by year
- 2026: 91 · 2025: 112 · 2024: 111 · 2023: 101 · 2022: 99 · 2021: 49 · 2020: 2
- FWCI
- 32.79
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 376 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- North Dakota State University
- Cancer Prevention and Research Institute of Texas (RP150231, P01CA117969)
- University of Texas MD Anderson Cancer Center
- National Cancer Institute (P30CA16672)
- Topics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Keywords
- type I collagen, myofibroblasts, alpha-smooth muscle actin, pancreatic ductal adenocarcinoma, tumor immunosuppression, T cells, CXCR2, CCR2, tumor stroma, tumor progression
- MeSH terms
- Animals, Disease Models, Animal, Pancreatic Neoplasms, CD8-Positive T-Lymphocytes, Carcinoma, Pancreatic Ductal, Collagen Type I, Cell Line, Tumor, Mice, Myofibroblasts, Pancreatic Stellate Cells, Tumor Microenvironment
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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