The DOI matches its Crossref record; 59 of the 59 references it cites were found in a registry or an index.
Impact of Epithelial–Stromal Interactions on Peritumoral Fibroblasts in Ductal Carcinoma in Situ
Open accessAbstract
Background: A better definition of biomarkers and biological processes related to local recurrence and disease progression is highly warranted for ductal breast carcinoma in situ (DCIS). Stromal–epithelial interactions are likely of major importance for the biological, clinical, and pathological distinctions between high- and low-risk DCIS cases. Methods: Stromal platelet derived growth factor receptor (PDGFR) was immunohistochemically assessed in two DCIS patient cohorts (n = 458 and n = 80). Cox proportional hazards models were used to calculate the hazard ratios of recurrence. The molecular mechanisms regulating stromal PDGFR expression were investigated in experimental in vitro co-culture systems of DCIS cells and fibroblasts and analyzed using immunoblot and quantitative real-time PCR. Knock-out of JAG1 in DCIS cells and NOTCH2 in fibroblasts was obtained through CRISPR/Cas9. Experimental data were validated by mammary fat pad injection of DCIS and DCIS-JAG1 knock-out cells (10 mice per group). All statistical tests were two-sided. Results: PDGFRα(low)/PDGFRβ(high) fibroblasts were associated with increased risk for recurrence in DCIS (univariate hazard ratio = 1.59, 95% confidence interval [CI] = 1.02 to 2.46; P = .04 Wald test; multivariable hazard ratio = 1.78, 95% CI = 1.07 to 2.97; P = .03). Tissue culture and mouse model studies indicated that this fibroblast phenotype is induced by DCIS cells in a cell contact-dependent manner. Epithelial Jagged1 and fibroblast Notch2 were identified through loss-of-function studies as key juxtacrine signaling components driving the formation of the poor prognosis-associated fibroblast phenotype. Conclusions: A PDGFRα(low)/PDGFRβ(high) fibroblast subset was identified as a marker for high-risk DCIS. The Jagged-1/Notch2/PDGFR stroma–epithelial pathway was described as a novel signaling mechanism regulating this poor prognosis-associated fibroblast subset. In general terms, the study highlights epithelial–stromal crosstalk in DCIS and contributes to ongoing efforts to define clinically relevant fibroblast subsets and their etiology.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
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?
In the citing paper
“Contact between cancer cells and fibroblasts can promote the CAF phenotype in breast cancer through Notch signalling55”
From A framework for advancing our understanding of cancer-associated fibroblasts (2020) · cites this paper as [55]
Citations
Cites
The biology and function of fibroblasts in cancer
Kalluri, R. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2016.73 · Cited by 4,366
Özdemir, B. C., Pentcheva-Hoang, T., Carstens, J. L., Zheng, X., Wu, C.-C., Simpson, T. R., Laklai, H., Sugimoto, H., Kahlert, C., Novitskiy, S. V., et al. (2014) · Cancer Cell · doi:10.1016/j.ccr.2014.04.005 · Cited by 2,681
Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer
Öhlund, D., Handly-Santana, A., Biffi, G., Elyada, E., Almeida, A. S., Ponz-Sarvise, M., Corbo, V., Oni, T. E., Hearn, S. A., Lee, E. J., et al. (2017) · Journal of Experimental Medicine · doi:10.1084/jem.20162024 · Cited by 2,590
Stromal Elements Act to Restrain, Rather Than Support, Pancreatic Ductal Adenocarcinoma
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., et al. (2014) · Cancer Cell · doi:10.1016/j.ccr.2014.04.021 · Cited by 2,085
Cox, T. R., & Erler, J. T. (2011) · Disease Models & Mechanisms · doi:10.1242/dmm.004077 · Cited by 1,569
GAGE: generally applicable gene set enrichment for pathway analysis
Luo, W., Friedman, M. S., Shedden, K., Hankenson, K. D., & Woolf, P. J. (2009) · BMC Bioinformatics · doi:10.1186/1471-2105-10-161 · Cited by 1,333
Induction of Cell Migration by Matrix Metalloprotease-2 Cleavage of Laminin-5
Giannelli, G., Falk-Marzillier, J., Schiraldi, O., Stetler-Stevenson, W. G., & Quaranta, V. (1997) · Science · doi:10.1126/science.277.5323.225 · Cited by 1,221
The tumour-induced systemic environment as a critical regulator of cancer progression and metastasis
McAllister, S. S., & Weinberg, R. A. (2014) · Nature Cell Biology · doi:10.1038/ncb3015 · Cited by 975
Rosen, P. P. (1997) · Cited by 820
Exosome Transfer from Stromal to Breast Cancer Cells Regulates Therapy Resistance Pathways
Boelens, M. C., Wu, T. J., Nabet, B. Y., Xu, B., Qiu, Y., Yoon, T., Azzam, D. J., Victor, C. T.-S., Wiemann, B. Z., Ishwaran, H., et al. (2014) · Cell · doi:10.1016/j.cell.2014.09.051 · Cited by 819
Gene expression profiling of the tumor microenvironment during breast cancer progression
Ma, X., Dahiya, S. M., Richardson, E., Erlander, M. G., & Sgroi, D. C. (2009) · Breast Cancer Research · doi:10.1186/bcr2222 · Cited by 630
Ductal Carcinoma In Situ of the Breast: A Systematic Review of Incidence, Treatment, and Outcomes
Virnig, B. A., Tuttle, T. M., Shamliyan, T., & Kane, R. L. (2010) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djp482 · Cited by 610
LOX-Mediated Collagen Crosslinking Is Responsible for Fibrosis-Enhanced Metastasis
Cox, T. R., Bird, D., Baker, A.-M., Barker, H. E., Ho, M. W.-Y., Lang, G., & Erler, J. T. (2013) · Cancer Research · doi:10.1158/0008-5472.can-12-2233 · Cited by 571
Cancer-associated fibroblasts and tumor growth – bystanders turning into key players
Östman, A., & Augsten, M. (2009) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2009.01.003 · Cited by 555
Self-citationRegulation of In Situ to Invasive Breast Carcinoma Transition
Hu, M., Yao, J., Carroll, D. K., Weremowicz, S., Chen, H., Carrasco, D. R., Richardson, A. L., Violette, S. M., Nikolskaya, T., Nikolsky, Y., et al. (2008) · Cancer Cell · doi:10.1016/j.ccr.2008.03.007 · Cited by 513
Grases, P. J. (2002) · Progresos de Obstetricia y Ginecología · doi:10.1016/s0304-5013(02)75784-1 · Cited by 499
Therapeutic modulation of Notch signalling — are we there yet?
Andersson, E. R., & Lendahl, U. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4252 · Cited by 463
Self-citationInhibition of PDGF receptor signaling in tumor stroma enhances antitumor effect of chemotherapy.
Pietras, K., Rubin, K., Sjöblom, T., Buchdunger, E., Sjöquist, M., Heldin, C., & Östman, A. (2002) · PubMed · Cited by 433
Self-citationSheldon, H., Heikamp, E., Turley, H., Dragovic, R., Thomas, P. H., Oon, C. E., Leek, R., Edelmann, M. J., Kessler, B. M., Sainson, R. C. A., et al. (2010) · Blood · doi:10.1182/blood-2009-08-239228 · Cited by 409
Liu, H., Kennard, S., & Lilly, B. (2009) · Circulation Research · doi:10.1161/circresaha.108.184846 · Cited by 293
Fibroblasts as architects of cancer pathogenesis
Marsh, T., Pietras, K., & McAllister, S. S. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2012.10.013 · Cited by 277
Self-citationCohen, M., Γεωργίου, Μ., Stevenson, N. L., Miodownik, M. A., & Baum, B. (2010) · Developmental Cell · doi:10.1016/j.devcel.2010.06.006 · Cited by 272
Paulsson, J., Sjöblom, T., Micke, P., Pontén, F., Landberg, G., Heldin, C., Bergh, J. C. S., Brennan, D. J., Jirström, K., & Östman, A. (2009) · American Journal Of Pathology · doi:10.2353/ajpath.2009.081030 · Cited by 269
Self-citationBasement membrane changes in breast cancer detected by immunohistochemical staining for laminin.
Albrechtsen, R., Nielsen, M., Wewer, U. M., Engvall, E., & Ruoslahti, E. I. (1981) · PubMed · Cited by 269
Progression from ductal carcinoma in situ to invasive breast cancer: Revisited
Cowell, C. F., Weigelt, B., Sakr, R. A., Ng, C. K. Y., Hicks, J. B., King, T. A., & Reis-Filho, J. S. (2013) · Molecular Oncology · doi:10.1016/j.molonc.2013.07.005 · Cited by 259
Immune Escape in Breast Cancer During In Situ to Invasive Carcinoma Transition
del Alcazar, C. R. G., Huh, S. J., Ekram, M. B., Trinh, A. C., Liu, L. L., de Beça, F. F., Zi, X., Kwak, M., Bergholtz, H., Su, Y., et al. (2017) · Cancer Discovery · doi:10.1158/2159-8290.cd-17-0222 · Cited by 255
Combined CSL and p53 downregulation promotes cancer-associated fibroblast activation
Procopio, M.-G., Laszlo, C., Al Labban, D., Kim, D. E., Bordignon, P., Jo, S.-H., Goruppi, S., Menietti, E., Ostano, P., Ala, U., et al. (2015) · Nature Cell Biology · doi:10.1038/ncb3228 · Cited by 223
Hu, M. S., Peluffo, G., Chen, H., Gelman, R. S., Schnitt, S. J., & Polyák, K. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0813306106 · Cited by 205
Furuhashi, M., Sjöblom, T., Abramsson, A., Ellingsen, J., Micke, P., Li, H., Folestad, E. B., Eriksson, U., Heuchel, R. L., Betsholtz, C., et al. (2004) · Cancer Research · doi:10.1158/0008-5472.can-03-1489 · Cited by 204
Self-citationJin, S., Hansson, E. M., Tikka, S., Lanner, F., Sahlgren, C., Farnebo, F. A., Baumann, M., Kalimo, H., & Lendahl, U. (2008) · Circulation Research · doi:10.1161/circresaha.107.167965 · Cited by 202
Self-citationSTC1 Expression By Cancer-Associated Fibroblasts Drives Metastasis of Colorectal Cancer
Peña, C., Céspedes, M. V., Lindh, M. B., Kiflemariam, S., Mezheyeuski, A., Edqvist, P.-H. D., Hägglöf, C., Birgisson, H., Bojmar, L., Jirström, K., et al. (2012) · Cancer Research · doi:10.1158/0008-5472.can-12-1875 · Cited by 185
Self-citationInvolvement of platelet‐derived growth factor ligands and receptors in tumorigenesis
Heldin, C. ‐., Lennartsson, J., & Westermark, B. (2018) · Journal of Internal Medicine · doi:10.1111/joim.12690 · Cited by 181
Previs, R. A., Coleman, R. L., Harris, A. L., & Sood, A. K. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-0809 · Cited by 178
Integrated Genomic and Transcriptomic Analysis of Ductal Carcinoma In situ of the Breast
Vincent‐Salomon, A., Lucchesi, C., Gruel, N., Raynal, V., Pierron, G., Goudefroye, R., Reyal, F., Radvanyi, F., Salmon, R. J., Thiery, J. P., et al. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-1465 · Cited by 159
Roswall, P., Bocci, M., Bartoschek, M., Li, H., Kristiansen, G., Jansson, S., Lehn, S., Sjölund, J., Reid, S., Larsson, C., et al. (2018) · Nature Medicine · doi:10.1038/nm.4494 · Cited by 155
Self-citationStromal caveolin-1 levels predict early DCIS progression to invasive breast cancer
Witkiewicz, A. K., Dasgupta, A., Nguyen, K., Liu, C., Kovatich, A. J., Schwartz, G. F., Pestell, R. G., Sotgia, F., Rui, H., & Lisanti, M. P. (2009) · Cancer Biology & Therapy · doi:10.4161/cbt.8.11.8874 · Cited by 128
Cohort Profile: The Karolinska Mammography Project for Risk Prediction of Breast Cancer (KARMA)
Gabrielson, M., Eriksson, M., Hammarström, M., Borgquist, S., Leifland, K., Czene, K., & Hall, P. N. (2016) · International Journal of Epidemiology · doi:10.1093/ije/dyw357 · Cited by 120
Self-citationWide Distribution of Laminin-5 γ2 Chain in Basement Membranes of Various Human Tissues
Mizushima, H., Koshikawa, N., Moriyama, K., Takamura, H., Nagashima, Y., Hirahara, F., & Miyazaki, K. (1998) · Hormone Research in Paediatrics · doi:10.1159/000053118 · Cited by 111
Hägglöf, C., Hammarsten, P., Josefsson, A., Stattin, P. E., Paulsson, J., Bergh, A. R. J., & Östman, A. (2010) · PLoS ONE · doi:10.1371/journal.pone.0010747 · Cited by 109
Self-citationEhnman, M., Missiaglia, E., Folestad, E. B., Selfe, J., Strell, C., Thway, K., Brodin, B. A., Pietras, K., SHIPLEY, J. M., Östman, A., et al. (2013) · Cancer Research · doi:10.1158/0008-5472.can-12-1646 · Cited by 98
Self-citationNotch modulates VEGF action in endothelial cells by inducing Matrix Metalloprotease activity
Funahashi, Y., Shawber, C. J., Sharma, A., Kanamaru, E., Choi, Y. K., & Kitajewski, J. (2011) · Vascular Cell · doi:10.1186/2045-824x-3-2 · Cited by 94
Östman, A. (2017) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2017.09.022 · Cited by 90
Self-citationJansson, S., Aaltonen, K. E., Bendahl, P., Falck, A., Karlsson, M. E., Pietras, K., & Rydén, L. (2018) · Breast Cancer Research and Treatment · doi:10.1007/s10549-018-4664-7 · Cited by 88
Self-citationNordby, Y., Richardsen, E. H., Rakaee, M., Ness, N., Dønnem, T., Patel, H., Busund, L., Bremnes, R. M., & Andersen, S. (2017) · Scientific Reports · doi:10.1038/srep43378 · Cited by 76
Johnson, C. E., Gorringe, K. L., Thompson, E. R., Opeskin, K., Boyle, S. E., Wang, Y.-K., Hill, P., Mann, G. B., & Campbell, I. (2011) · Breast Cancer Research and Treatment · doi:10.1007/s10549-011-1835-1 · Cited by 67
Ductal carcinoma in situ of the breast: the importance of morphologic and molecular interactions
Gargano, S., Bombonati, A., & Palazzo, J. (2015) · Human Pathology · doi:10.1016/j.humpath.2015.11.003 · Cited by 57
Second events following ductal carcinoma in situ of the breast: a register-based cohort study
Falk, R. S., Hofvind, S. S. H., Skaane, P., & Haldorsen, T. (2011) · Breast Cancer Research and Treatment · doi:10.1007/s10549-011-1531-1 · Cited by 56
Corvigno, S., Wisman, G. B. A., Mezheyeuski, A., van der Zee, A. G. J., Nijman, H. W., Åvall-Lundqvist, E. H., Östman, A., & Dahlstrand, H. M. (2016) · Oncotarget · doi:10.18632/oncotarget.7613 · Cited by 48
Self-citationHigh expression of stromal PDGFRβ is associated with reduced benefit of tamoxifen in breast cancer
Paulsson, J., Rydén, L., Strell, C., Frings, O., Tobin, N. P., Fornander, T., Bergh, J. C. S., Landberg, G., Stål, O., & Östman, A. (2016) · The Journal of Pathology Clinical Research · doi:10.1002/cjp2.56 · Cited by 43
Self-citationMartins, D. F., de Beça, F. F., Sousa, B., Baltazar, F., Paredes, J., & Schmitt, F. C. (2013) · Cell Cycle · doi:10.4161/cc.25794 · Cited by 42
Zhou, W., Jirström, K., Johansson, C., Amini, R., BLOMQVIST, C. P., Agbaje, O. F., & Wärnberg, F. (2010) · BMC Cancer · doi:10.1186/1471-2407-10-653 · Cited by 41
Self-citationBlaise, R., Mahjoub, M., Salvat, C., Barbe, U., Brou, C., Corvol, M. T., Savouret, J., Rannou, F., Berenbaum, F., & Bausero, P. (2009) · Arthritis & Rheumatism · doi:10.1002/art.24250 · Cited by 39
Identifying progression predictors of breast ductal carcinoma in situ
Yeong, J. P.-S., Thike, A. A., Tan, P. H., & Iqbal, J. (2016) · Journal of Clinical Pathology · doi:10.1136/jclinpath-2016-204154 · Cited by 36
Loss of CSL Unlocks a Hypoxic Response and Enhanced Tumor Growth Potential in Breast Cancer Cells
Braune, E.-B., Tsoi, Y. L., Phoon, Y. P., Landor, S. K.-J., Cascales, H. S., Ramsköld, D., Deng, Q., Lindqvist, A., Lian, X. L., Sahlgren, C., et al. (2016) · Stem Cell Reports · doi:10.1016/j.stemcr.2016.03.004 · Cited by 35
Self-citationKarlsson, E., Sandelin, K., Appelgren, J., Zhou, W., Jirström, K., Bergh, J. C. S., & Wärnberg, F. (2013) · European Journal of Cancer · doi:10.1016/j.ejca.2013.10.020 · Cited by 29
Self-citationWadsten, C., Heyman, H., Holmqvist, M., Ahlgren, J., Lambe, M. P., Sund, M., & Wärnberg, F. (2016) · Acta Oncologica · doi:10.1080/0284186x.2016.1211317 · Cited by 21
Self-citationZhou, W., Johansson, C., Jirström, K., Ringberg, A., BLOMQVIST, C. P., Amini, R., Fjällskog, M.-L., & Wärnberg, F. (2013) · International Journal of Breast Cancer · doi:10.1155/2013/582134 · Cited by 19
Self-citationA contribution to the natural history of breast cancer
Tulusan, A. H., Grünsteidel, W., Ramming, I., & Egger, H. (1982) · Archives of Gynecology and Obstetrics · doi:10.1007/bf02110120 · Cited by 16
Rajan, P. B., & Perry, R. H. (1995) · The Breast Journal · doi:10.1111/j.1524-4741.1995.tb00255.x · Cited by 3
Cited by
Sorted by citations
A framework for advancing our understanding of cancer-associated fibroblasts
Sahai, E., Astsaturov, I., Cukierman, E., DeNardo, D. G., Egeblad, M., Evans, R. M., Fearon, D., Greten, F. R., Hingorani, S. R., Hunter, T., et al. (2020) · Nature Reviews Cancer · doi:10.1038/s41568-019-0238-1 · Cited by 3,863
Notch signaling pathway: architecture, disease, and therapeutics
Zhou, B., Lin, W., Long, Y., Yang, Y., Zhang, H., Wu, K., & Chu, Q. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-00934-y · Cited by 1,216
Single-cell analysis reveals fibroblast clusters linked to immunotherapy resistance in cancer.
Kieffer, Y., Hocine, H. R., Gentric, G., Pelon, F., Bernard, C., Bourachot, B., Lameiras, S., Albergante, L., Bonneau, C., Guyard, A., et al. (2020) · Cancer Discovery · doi:10.1158/2159-8290.cd-19-1384 · Cited by 910
Tumor initiation and early tumorigenesis: molecular mechanisms and interventional targets
Zhang, S., Xiao, X., Yi, Y., Wang, X., Zhu, L., Shen, Y., Lin, D., & Wu, C. H. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01848-7 · Cited by 463
Pelon, F., Bourachot, B., Kieffer, Y., Magagna, I., Mermet‐Meillon, F., Bonnet, I., Costa, A., Givel, A.-M., Atieh, Y., Barbazán, J., et al. (2020) · Nature Communications · doi:10.1038/s41467-019-14134-w · Cited by 404
Metadata
- Authors
- Strell, C., Paulsson, J., Jin, S.-B., Tobin, N. P., Mezheyeuski, A., Roswall, P., Mutgan, C., Mitsios, N., Johansson, H., Wickberg, S. M., Svedlund, J., Nilsson, M., Hall, P., Mulder, J., Radisky, D. C., Pietras, K., Bergh, J., Lendahl, U., Wärnberg, F., & Östman, A.
- Affiliations
- Stockholm University (SE)
- Karolinska Institutet (SE)
- Lund University (SE)
- Uppsala University (SE)
- Mayo Clinic in Florida (US)
- Corresponding author
- Strell, Carina
- ORCID
- Venue
- JNCI: Journal of the National Cancer Institute
- Publisher
- Oxford University Press (OUP)
- Published
- 2019-02-28
- Volume
- 111
- Issue
- 9
- Pages
- 983-995
- ISSN
- 0027-8874 (ISSN-L)
- 1460-2105
- PMC
- PMC6748730
- OpenAlex
- W2920295895
- Cited by
- 158
- References
- 59
- Citations by year
- 2026: 12 · 2025: 13 · 2024: 25 · 2023: 19 · 2022: 36 · 2021: 30 · 2020: 19 · 2019: 4
- FWCI
- 4.01
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- JNCI Journal of the National Cancer Institute (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- Swedish Cancer Society (150895)
- Swedish Research Council (349–2006-160)
- Radiumhemmets forskningsfonder, EU Caffein ITN network (3047/12)
- BRECT network of Karolinska Institutet
- Stockholm County Council
- Comprehensive Cancer Consortium
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
- Health Sciences › Medicine › Pathology and Forensic Medicine › Breast Lesions and Carcinomas
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Keywords
- ductal carcinoma in situ, stromal-epithelial interactions, PDGFR, PDGFRA, PDGFRβ, fibroblast phenotype, local recurrence, JAG1, Notch2, juxtacrine signaling, prognostic factors, breast cancer
- MeSH terms
- Cancer-Associated Fibroblasts, Adult, Aged, Aged, 80 and over, Animals, Breast Neoplasms, Carcinoma, Intraductal, Noninfiltrating, Cell Communication, Disease Models, Animal, Epithelial Cells, Female, Humans, Immunohistochemistry, Middle Aged, Prognosis, Biomarkers, Tumor, Stromal Cells, Receptors, Platelet-Derived Growth Factor, Coculture Techniques, Computational Biology, Gene Expression Profiling, Cell Line, Tumor, Mice, Neoplasm Grading
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
