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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“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]
Experimental — accuracy not yet measuredIn the citing paper
“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]
In the citing paper
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Hallmarks of Cancer: The Next Generation
Hanahan, D., & Weinberg, R. A. (2011) · Cell · doi:10.1016/j.cell.2011.02.013 · Cited by 66,590
Olive, K. P., Jacobetz, M. A., Davidson, C. J., Gopinathan, A., McIntyre, D., Honess, D., Madhu, B., Goldgraben, M. A., Caldwell, M. E., Allard, D., et al. (2009) · Science · doi:10.1126/science.1171362 · Cited by 3,170
Self-citationHingorani, S. R., Wang, L., Multani, A. S., Combs, C., Deramaudt, T. B., Hruban, R. H., Rustgi, A. K., Chang, S., & Tuveson, D. A. (2005) · Cancer Cell · doi:10.1016/j.ccr.2005.04.023 · Cited by 2,609
Provenzano, P. P., Cuevas, C., Chang, A. E., Goel, V. K., Von Hoff, D. D., & Hingorani, S. R. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.01.007 · Cited by 2,195
EMT and Dissemination Precede Pancreatic Tumor Formation
Rhim, A. D., Mirek, E. T., Aiello, N. M., Maitra, A., Bailey, J. M., McAllister, F., Reichert, M., Beatty, G. L., Rustgi, A. K., Vonderheide, R. H., et al. (2012) · Cell · doi:10.1016/j.cell.2011.11.025 · Cited by 2,136
Self-citationThe role of autophagy in cancer development and response to therapy
Kondo, Y., Kanzawa, T., Sawaya, R. A., & Kondo, S. (2005) · Nature reviews. Cancer · doi:10.1038/nrc1692 · Cited by 1,672
Hedgehog is an early and late mediator of pancreatic cancer tumorigenesis
Thayer, S. P., di Magliano, M. P., Heiser, P. W., Nielsen, C. M., Roberts, D. J., Lauwers, G. Y., Qi, Y., Gysin, S., Castillo, C. F. F.-D., Yajnik, V., et al. (2003) · Nature · doi:10.1038/nature02009 · Cited by 1,479
Hyaluronan impairs vascular function and drug delivery in a mouse model of pancreatic cancer
Jacobetz, M. A., Chan, D. S., Neesse, A., Bapiro, T. E., Cook, N., Frese, K. K., Feig, C., Nakagawa, T., Caldwell, M. E., Zecchini, H. I., et al. (2013) · Gut · doi:10.1136/gutjnl-2012-302529 · Cited by 1,120
Cancer-Associated Stromal Fibroblasts Promote Pancreatic Tumor Progression
Hwang, R. F., Moore, T. T., Arumugam, T., Ramachandran, V., Amos, K. D., Rivera, A. M., Ji, B., Evans, D. B., & Logsdon, C. D. (2008) · Cancer Research · doi:10.1158/0008-5472.can-07-5714 · Cited by 1,093
Iacobuzio-Donahue, C. A., Fu, B., Yachida, S., Luo, M., Abe, H., Henderson, C. M., Vilardell, F., Wang, Z., Keller, J. W., Banerjee, P., et al. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2008.17.7188 · Cited by 1,081
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Items 101–110 of 110
Leveraging microenvironmental synthetic lethalities to treat cancer
Metcalf, K. J., Alazzeh, A., Werb, Z., & Weaver, V. M. (2021) · Journal of Clinical Investigation · doi:10.1172/jci143765 · Cited by 42
Pentose conversions support the tumorigenesis of pancreatic cancer distant metastases
Bechard, M. E., Word, A. E., Tran, A. V., Liu, X., Locasale, J. W., & McDonald, O. G. (2018) · Oncogene · doi:10.1038/s41388-018-0346-5 · Cited by 35
Bechard, M. E., Smalling, R., Hayashi, A., Zhong, Y., Word, A. E., Campbell, S. L., Tran, A. V., Weiss, V. L., Iacobuzio-Donahue, C., Wellen, K. E., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-17839-5 · Cited by 33
Self-citationPDAC as an immune evasive disease: can 3D model systems aid to tackle this clinical problem?
Narayanan, S., Vicent, S., & Ponz-Sarvisé, M. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.787249 · Cited by 24
Liu, X., Gündel, B., Li, X., Liu, J., Wright, A., Löhr, M., Arvidsson, G., & Heuchel, R. (2021) · Translational Oncology · doi:10.1016/j.tranon.2021.101107 · Cited by 24
Qi, B., Crawford, A. J., Wojtynek, N. E., Talmon, G. A., Hollingsworth, M. A., Ly, Q. P., & Mohs, A. M. (2020) · Theranostics · doi:10.7150/thno.40688 · Cited by 18
Cancer-Associated Fibroblast Proteins as Potential Targets against Colorectal Cancers
Shah, R., Johnson, K. A., Lippert, A. E. L., Kraus, S. G., Emmerich, P. B., Pasch, C. A., Zhang, W., Matkowskyj, K. A., LeBeau, A. M., & Deming, D. A. (2024) · Cancers · doi:10.3390/cancers16183158 · Cited by 18
Vidimar, V., Park, M., Stubbs, C. K., Ingram, N. K., Qiang, W., Zhang, S., Gursel, D., Melnyk, R. A., & Satchell, K. J. F. (2022) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-21-0550 · Cited by 10
Brunel, A., Samain, R., Neuzillet, C., & Bousquet, C. (2018) · Translational Cancer Research · doi:10.21037/tcr.2018.06.09 · Cited by 5
Liang, C.-H., Ye, H., Xu, H., Fang, C., Lian, J.-P., Chen, Y.-Q., Wang, W.-T., & He, B. (2026) · Advanced Biotechnology · doi:10.1007/s44307-026-00141-8
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
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.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
