The DOI matches its Crossref record; 65 of the 65 references it cites were found in a registry or an index.
Macrophage-secreted granulin supports pancreatic cancer metastasis by inducing liver fibrosis
Open accessAbstract
Pancreatic ductal adenocarcinoma (PDAC) is a devastating metastatic disease for which better therapies are urgently needed. Macrophages enhance metastasis in many cancer types; however, the role of macrophages in PDAC liver metastasis remains poorly understood. Here we found that PDAC liver metastasis critically depends on the early recruitment of granulin-secreting inflammatory monocytes to the liver. Mechanistically, we demonstrate that granulin secretion by metastasis-associated macrophages (MAMs) activates resident hepatic stellate cells (hStCs) into myofibroblasts that secrete periostin, resulting in a fibrotic microenvironment that sustains metastatic tumour growth. Disruption of MAM recruitment or genetic depletion of granulin reduced hStC activation and liver metastasis. Interestingly, we found that circulating monocytes and hepatic MAMs in PDAC patients express high levels of granulin. These findings suggest that recruitment of granulin-expressing inflammatory monocytes plays a key role in PDAC metastasis and may serve as a potential therapeutic target for PDAC liver metastasis.
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“for example, granulin produced by macrophages promotes the activation of a fibrotic environment in liver metastases76,77.”
From A framework for advancing our understanding of cancer-associated fibroblasts (2020) · cites this paper as [76]
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Metadata
- Authors
- Nielsen, S. R., Quaranta, V., Linford, A., Emeagi, P., Rainer, C., Santos, A., Ireland, L., Sakai, T., Sakai, K., Kim, Y.-S., Engle, D., Campbell, F., Palmer, D., Ko, J. H., Tuveson, D. A., Hirsch, E., Mielgo, A., & Schmid, M. C.
- Affiliations
- University of Liverpool (GB)
- Korea Research Institute of Bioscience and Biotechnology (KR)
- Cold Spring Harbor Laboratory (US)
- Memorial Sloan Kettering Cancer Center (US)
- University of Turin (IT)
- Corresponding author
- Schmid, Michael C.
- ORCID
- Venue
- Nature Cell Biology
- Published
- 2016-04-18
- Volume
- 18
- Issue
- 5
- Pages
- 549-560
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- PMC
- PMC4894551
- OpenAlex
- W2336583997
- Cited by
- 441
- References
- 65
- Citations by year
- 2026: 25 · 2025: 39 · 2024: 51 · 2023: 58 · 2022: 43 · 2021: 58 · 2020: 45 · 2019: 51 · 2018: 36 · 2017: 25 · 2016: 9
- FWCI
- 19.59
- Type
- journal article
- Language
- en
- Update notices
- erratum (2016-06-28)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (submittedVersion)
- KRIBB Repository (submittedVersion)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion, other-oa)
- Funders
- Wellcome Trust (102521/Z/13/Z, 102521)
- National Institutes of Health (5p30ca045508-35)
- Medical Research Council (MR/L000512/1)
- National Cancer Institute (T32CA148056, P30-CA045508, P30CA008748)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Keywords
- granulin, pancreatic ductal adenocarcinoma, liver metastasis, inflammatory monocytes, hepatic stellate cells, liver fibrosis, periostin, myofibroblast activation, tumor microenvironment, macrophage recruitment
- MeSH terms
- Progranulins, Adenocarcinoma, Animals, Humans, Inflammation, Liver Cirrhosis, Liver Neoplasms, Macrophages, Monocytes, Neoplasm Metastasis, Pancreatic Neoplasms, Carcinoma, Pancreatic Ductal, Intercellular Signaling Peptides and Proteins, Cell Line, Tumor, Cell Proliferation, Mice, Hepatic Stellate Cells, Myofibroblasts
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