The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.
Stromal Elements Act to Restrain, Rather Than Support, Pancreatic Ductal Adenocarcinoma
Open accessAbstract
Sonic hedgehog (Shh), a soluble ligand overexpressed by neoplastic cells in pancreatic ductal adenocarcinoma (PDAC), drives formation of a fibroblast-rich desmoplastic stroma. To better understand its role in malignant progression, we deleted Shh in a well-defined mouse model of PDAC. As predicted, Shh-deficient tumors had reduced stromal content. Surprisingly, such tumors were more aggressive and exhibited undifferentiated histology, increased vascularity, and heightened proliferation--features that were fully recapitulated in control mice treated with a Smoothened inhibitor. Furthermore, administration of VEGFR blocking antibody selectively improved survival of Shh-deficient tumors, indicating that Hedgehog-driven stroma suppresses tumor growth in part by restraining tumor angiogenesis. Together, these data demonstrate that some components of the tumor stroma can act to restrain tumor growth.
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“subsequent preclinical studies that suppressed in the long term the CAF subset known to be Hedgehog responsive also demonstrated more rapid PDAC progression35,36.”
From A framework for advancing our understanding of cancer-associated fibroblasts (2020) · cites this paper as [35]
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“preclinical studies suggesting that the non-specific targeting or deletion of stromal fibroblasts may not enhance tumour control35,36.”
From A framework for advancing our understanding of cancer-associated fibroblasts (2020) · cites this paper as [35]
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“Furthermore, high infiltration of M2 macrophages in tumor tissues is associated with poor clinical prognosis.[ 28 ]”
From 3D Biomimetic Models to Reconstitute Tumor Microenvironment In Vitro: Spheroids, Organoids, and Tumor‐on‐a‐Chip (2023) · cites this paper as [28]
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“One notable example of an ultimately unsuccessful but informative clinical paradigm came by way of a series of pre-clinical studies proposing the efficacy of systemic therapy would improve through efforts to penetrate the dense fibrosis and high interstitial pressure promoted by the CAFs in pancreatic tumors140,158.”
From Pancreatic cancer: Advances and challenges (2023) · cites this paper as [158]
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“However, CAF depletion has also been shown to reduce infiltrating immune cells, leading to tumor progression [100].”
From Tumor microenvironment signaling and therapeutics in cancer progression (2023) · cites this paper as [100]
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Metadata
- Authors
- Rhim, A. D., Oberstein, P. E., Thomas, D. H., Mirek, E. T., Palermo, C. F., Sastra, S. A., Dekleva, E. N., Saunders, T., Becerra, C. P., Tattersall, I. W., Westphalen, C. B., Kitajewski, J., Fernandez-Barrena, M. G., Fernandez-Zapico, M. E., Iacobuzio-Donahue, C., Olive, K. P., & Stanger, B. Z.
- Affiliations
- University of Michigan (US)
- Columbia University Irving Medical Center (US)
- University of Pennsylvania (US)
- Johns Hopkins University (US)
- Corresponding author
- Olive, Kenneth P.
- Stanger, Ben Z.
- ORCID
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2014-06
- Volume
- 25
- Issue
- 6
- Pages
- 735-747
- ISSN
- 1535-6108 (ISSN-L)
- PMC
- PMC4096698
- OpenAlex
- W1996912024
- Cited by
- 2,085
- References
- 41
- Citations by year
- 2026: 158 · 2025: 131 · 2024: 149 · 2023: 169 · 2022: 226 · 2021: 225 · 2020: 200 · 2019: 157 · 2018: 162 · 2017: 161 · 2016: 179 · 2015: 122 · 2014: 45
- FWCI
- 81.22
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL112626)
- National Cancer Institute (CA177857, CA 136526, CA169123, R01CA157980, CA046952, CA157980, R01CA177857, R01CA169123, R01CA136526, T32CA009503, P30CA015083, P30CA013696, P30CA016520)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK034933, DK 034933, DP2DK083111, K08DK088945, DK088945, DK083111, R01DK083355, DK083355, P30DK084567, P30DK050306)
- National Center for Research Resources (S10RR025686, S10RR025482)
- Topics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Hedgehog Signaling Pathway Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Keywords
- pancreatic ductal adenocarcinoma, Sonic hedgehog, Hedgehog signaling, tumor stroma, desmoplasia, Smoothened inhibitors, tumor angiogenesis, tumor vascularity, tumor cell proliferation, tumor differentiation
- MeSH terms
- Animals, Antibodies, Monoclonal, Disease Models, Animal, Humans, Immunoglobulin G, Mice, Transgenic, Pancreatic Neoplasms, Random Allocation, Signal Transduction, Stromal Cells, Disease Progression, Carcinoma, Pancreatic Ductal, Receptors, Vascular Endothelial Growth Factor, Cell Line, Tumor, Mice, Hedgehog Proteins, Gene Knockdown Techniques
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