The DOI matches its Crossref record; 44 of the 44 references it cites were found in a registry or an index.
Macrophage-secreted cytokines drive pancreatic acinar-to-ductal metaplasia through NF-κB and MMPs
Open accessAbstract
In response to inflammation, pancreatic acinar cells can undergo acinar-to-ductal metaplasia (ADM), a reprogramming event that induces transdifferentiation to a ductlike phenotype and, in the context of additional oncogenic stimulation, contributes to development of pancreatic cancer. The signaling mechanisms underlying pancreatitis-inducing ADM are largely undefined. Our results provide evidence that macrophages infiltrating the pancreas drive this transdifferentiation process. We identify the macrophage-secreted inflammatory cytokines RANTES and tumor necrosis factor α (TNF) as mediators of such signaling. Both RANTES and TNF induce ADM through activation of nuclear factor κB and its target genes involved in regulating survival, proliferation, and degradation of extracellular matrix. In particular, we identify matrix metalloproteinases (MMPs) as targets that drive ADM and provide in vivo data suggesting that MMP inhibitors may be efficiently applied to block pancreatitis-induced ADM in therapy.
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Cites
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Self-citationInflammation meets cancer, with NF-κB as the matchmaker
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Pancreatic cancer biology and genetics
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Activation of the IκBα Kinase Complex by MEKK1, a Kinase of the JNK Pathway
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Cited by
Tumor-Associated Macrophages: From Mechanisms to Therapy
Noy, R., & Pollard, J. W. (2014) · Immunity · doi:10.1016/j.immuni.2014.06.010 · Cited by 4,089
Type 3c (pancreatogenic) diabetes mellitus secondary to chronic pancreatitis and pancreatic cancer
Hart, P. A., Bellin, M. D., Andersen, D. K., Bradley, D., Cruz-Monserrate, Z., Forsmark, C. E., Goodarzi, M. O., Habtezion, A., Korc, M., Kudva, Y. C., et al. (2016) · The Lancet Gastroenterology & Hepatology · doi:10.1016/s2468-1253(16)30106-6 · Cited by 551
Broadening the Impact of Immunotherapy to Pancreatic Cancer: Challenges and Opportunities
Balachandran, V. P., Beatty, G. L., & Dougan, S. K. (2019) · Gastroenterology · doi:10.1053/j.gastro.2018.12.038 · Cited by 444
Acinar cell plasticity and development of pancreatic ductal adenocarcinoma
Storz, P. (2017) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2017.12 · Cited by 389
Self-citationMacrophage Polarization and Reprogramming in Acute Inflammation: A Redox Perspective
Pérez, S., & Rius-Pérez, S. (2022) · Antioxidants · doi:10.3390/antiox11071394 · Cited by 312
Metadata
- Authors
- Liou, G.-Y., Döppler, H., Necela, B., Krishna, M., Crawford, H. C., Raimondo, M., & Storz, P.
- Venue
- Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2013-08-05
- Volume
- 202
- Issue
- 3
- Pages
- 563-577
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- OpenAlex
- W2123852594
- Cited by
- 294
- References
- 44
- FWCI
- 10.59
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Liou, G.-Y., Döppler, H., Necela, B., Krishna, M., Crawford, H. C., Raimondo, M., & Storz, P. (2013). Macrophage-secreted cytokines drive pancreatic acinar-to-ductal metaplasia through NF-κB and MMPs. Journal of Cell Biology. https://doi.org/10.1083/jcb.201301001
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