Regulation of metaplasia and dysplasia in the stomach by the stromal microenvironment.
Journal
Experimental & molecular medicine
ISSN: 2092-6413
Titre abrégé: Exp Mol Med
Pays: United States
ID NLM: 9607880
Informations de publication
Date de publication:
03 Jun 2024
03 Jun 2024
Historique:
received:
30
11
2023
accepted:
03
03
2024
revised:
03
03
2024
medline:
3
6
2024
pubmed:
3
6
2024
entrez:
2
6
2024
Statut:
aheadofprint
Résumé
Research on the microenvironment associated with gastric carcinogenesis has focused on cancers of the stomach and often underestimates premalignant stages such as metaplasia and dysplasia. Since epithelial interactions with T cells, macrophages, and type 2 innate lymphoid cells (ILC2s) are indispensable for the formation of precancerous lesions in the stomach, understanding the cellular interactions that promote gastric precancer warrants further investigation. Although various types of immune cells have been shown to play important roles in gastric carcinogenesis, it remains unclear how stromal cells such as fibroblasts influence epithelial transformation in the stomach, especially during precancerous stages. Fibroblasts exist as distinct populations across tissues and perform different functions depending on the expression patterns of cell surface markers and secreted factors. In this review, we provide an overview of known microenvironmental components in the stroma with an emphasis on fibroblast subpopulations and their roles during carcinogenesis in tissues including breast, pancreas, and stomach. Additionally, we offer insights into potential targets of tumor-promoting fibroblasts and identify open areas of research related to fibroblast plasticity and the modulation of gastric carcinogenesis.
Identifiants
pubmed: 38825636
doi: 10.1038/s12276-024-01240-z
pii: 10.1038/s12276-024-01240-z
doi:
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)
ID : CA009592
Organisme : U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)
ID : CA272687
Organisme : U.S. Department of Veterans Affairs (Department of Veterans Affairs)
ID : IBX000930
Organisme : U.S. Department of Defense (United States Department of Defense)
ID : CA190172
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : DK101332
Informations de copyright
© 2024. The Author(s).
Références
Giroux, V. & Rustgi, A. K. Metaplasia: tissue injury adaptation and a precursor to the dysplasia-cancer sequence. Nat. Rev. Cancer 17, 594–604 (2017).
pubmed: 28860646
pmcid: 5998678
doi: 10.1038/nrc.2017.68
Goldenring, J. R. & Mills, J. C. Cellular plasticity, reprogramming, and regeneration: metaplasia in the stomach and beyond. Gastroenterology 162, 415–430 (2022).
pubmed: 34728185
doi: 10.1053/j.gastro.2021.10.036
Schmidt, P. H. et al. Identification of a metaplastic cell lineage associated with human gastric adenocarcinoma. Lab. Investig. 79, 639–646 (1999).
pubmed: 10378506
Fox, J. G. et al. Hypertrophic gastropathy in Helicobacter felis-infected wild-type C57BL/6 mice and p53 hemizygous transgenic mice. Gastroenterology 110, 155–166 (1996).
pubmed: 8536852
doi: 10.1053/gast.1996.v110.pm8536852
Lee, S. H. et al. Up-regulation of Aquaporin 5 defines spasmolytic polypeptide-expressing metaplasia and progression to incomplete intestinal metaplasia. Cell Mol. Gastroenterol. Hepatol. 13, 199–217 (2022).
pubmed: 34455107
doi: 10.1016/j.jcmgh.2021.08.017
Shah, S. C., Gawron, A. J., Mustafa, R. A. & Piazuelo, M. B. Histologic subtyping of gastric intestinal metaplasia: overview and considerations for clinical practice. Gastroenterology 158, 745–750 (2020).
pubmed: 31887261
doi: 10.1053/j.gastro.2019.12.004
Choi, E., Hendley, A. M., Bailey, J. M., Leach, S. D. & Goldenring, J. R. Expression of activated ras in gastric chief cells of mice leads to the full spectrum of metaplastic lineage transitions. Gastroenterology 150, 918–930.e913 (2016).
pubmed: 26677984
doi: 10.1053/j.gastro.2015.11.049
Goldenring, J. R., Nam, K. T., Wang, T. C., Mills, J. C. & Wright, N. A. Spasmolytic polypeptide-expressing metaplasia and intestinal metaplasia: time for reevaluation of metaplasias and the origins of gastric cancer. Gastroenterology 138, 2207–2210 (2010).
pubmed: 20450866
doi: 10.1053/j.gastro.2010.04.023
Lauwers, G. Y. & Riddell, R. H. Gastric epithelial dysplasia. Gut 45, 784–790 (1999).
pubmed: 10517922
pmcid: 1727726
doi: 10.1136/gut.45.5.784
Riera, K. M. et al. Trop2 is upregulated in the transition to dysplasia in the metaplastic gastric mucosa. J. Pathol. 251, 336–347 (2020).
pubmed: 32432338
pmcid: 8010636
doi: 10.1002/path.5469
Lee, S. H. et al. Apposition of fibroblasts with metaplastic gastric cells promotes dysplastic transition. Gastroenterology 165, 374–390 (2023).
pubmed: 37196797
doi: 10.1053/j.gastro.2023.04.038
Blaser, M. J. & Parsonnet, J. Parasitism by the “slow” bacterium Helicobacter pylori leads to altered gastric homeostasis and neoplasia. J. Clin. Investig. 94, 4–8 (1994).
pubmed: 8040281
pmcid: 296275
doi: 10.1172/JCI117336
Yoshizawa, N. et al. Emergence of spasmolytic polypeptide-expressing metaplasia in Mongolian gerbils infected with Helicobacter pylori. Lab. Investig. 87, 1265–1276 (2007).
pubmed: 18004396
doi: 10.1038/labinvest.3700682
Nam, K. T. et al. Mature chief cells are cryptic progenitors for metaplasia in the stomach. Gastroenterology 139, 2028–2037.e2029 (2010).
pubmed: 20854822
doi: 10.1053/j.gastro.2010.09.005
Goldenring, J. R. et al. Reversible drug-induced oxyntic atrophy in rats. Gastroenterology 118, 1080–1093 (2000).
pubmed: 10833483
doi: 10.1016/S0016-5085(00)70361-1
Manning, E. H., Lapierre, L. A., Mills, J. C. & Goldenring, J. R. Tamoxifen acts as a parietal cell protonophore. Cell Mol. Gastroenterol. Hepatol. 10, 655–657.e651 (2020).
pubmed: 32361017
pmcid: 7474156
doi: 10.1016/j.jcmgh.2020.04.012
Nomura, S. et al. Alterations in gastric mucosal lineages induced by acute oxyntic atrophy in wild-type and gastrin-deficient mice. Am. J. Physiol. Gastrointest. Liver Physiol. 288, G362–375 (2005).
pubmed: 15647607
doi: 10.1152/ajpgi.00160.2004
Huh, W. J. et al. Tamoxifen induces rapid, reversible atrophy, and metaplasia in mouse stomach. Gastroenterology 142, 21–24.e27 (2012).
pubmed: 22001866
doi: 10.1053/j.gastro.2011.09.050
Caldwell, B., Meyer, A. R., Weis, J. A., Engevik, A. C. & Choi, E. Chief cell plasticity is the origin of metaplasia following acute injury in the stomach mucosa. Gut 71, 1068–1077 (2022).
pubmed: 34497145
doi: 10.1136/gutjnl-2021-325310
Min, J. et al. Heterogeneity and dynamics of active Kras-induced dysplastic lineages from mouse corpus stomach. Nat. Commun. 10, 5549 (2019).
pubmed: 31804471
pmcid: 6895174
doi: 10.1038/s41467-019-13479-6
Zhang, M. et al. Dissecting transcriptional heterogeneity in primary gastric adenocarcinoma by single cell RNA sequencing. Gut 70, 464–475 (2021).
pubmed: 32532891
doi: 10.1136/gutjnl-2019-320368
Kim, J. et al. Single-cell analysis of gastric pre-cancerous and cancer lesions reveals cell lineage diversity and intratumoral heterogeneity. NPJ Precis. Oncol. 6, 9 (2022).
pubmed: 35087207
pmcid: 8795238
doi: 10.1038/s41698-022-00251-1
Sathe, A. et al. Single-cell genomic characterization reveals the cellular reprogramming of the gastric tumor microenvironment. Clin. Cancer Res. 26, 2640–2653 (2020).
pubmed: 32060101
pmcid: 7269843
doi: 10.1158/1078-0432.CCR-19-3231
Fox, J. G. et al. Local and systemic immune responses in murine Helicobacter felis active chronic gastritis. Infect. Immun. 61, 2309–2315 (1993).
pubmed: 8500873
pmcid: 280850
doi: 10.1128/iai.61.6.2309-2315.1993
Osaki, L. H. et al. Interferon-gamma directly induces gastric epithelial cell death and is required for progression to metaplasia. J. Pathol. 247, 513–523 (2019).
pubmed: 30511397
pmcid: 6402979
doi: 10.1002/path.5214
El-Zaatari, M. et al. Aim2-mediated/IFN-beta-independent regulation of gastric metaplastic lesions via CD8+ T cells. JCI Insight 5, e94035 (2020).
pubmed: 32053518
pmcid: 7141403
doi: 10.1172/jci.insight.94035
Smythies, L. E. et al. Helicobacter pylori-induced mucosal inflammation is Th1 mediated and exacerbated in IL-4, but not IFN-gamma, gene-deficient mice. J. Immunol. 165, 1022–1029 (2000).
pubmed: 10878379
doi: 10.4049/jimmunol.165.2.1022
Roth, K. A., Kapadia, S. B., Martin, S. M. & Lorenz, R. G. Cellular immune responses are essential for the development of Helicobacter felis-associated gastric pathology. J. Immunol. 163, 1490–1497 (1999).
pubmed: 10415051
doi: 10.4049/jimmunol.163.3.1490
Ding, L. et al. Schlafen 4-expressing myeloid-derived suppressor cells are induced during murine gastric metaplasia. J. Clin. Investig. 126, 2867–2880 (2016).
pubmed: 27427984
pmcid: 4966326
doi: 10.1172/JCI82529
Petersen, C. P. et al. Macrophages promote progression of spasmolytic polypeptide-expressing metaplasia after acute loss of parietal cells. Gastroenterology 146, 1727–1738.e1728 (2014).
pubmed: 24534633
doi: 10.1053/j.gastro.2014.02.007
Wynn, T. A., Chawla, A. & Pollard, J. W. Macrophage biology in development, homeostasis and disease. Nature 496, 445–455 (2013).
pubmed: 23619691
pmcid: 3725458
doi: 10.1038/nature12034
Murray, P. J. & Wynn, T. A. Protective and pathogenic functions of macrophage subsets. Nat. Rev. Immunol. 11, 723–737 (2011).
pubmed: 21997792
pmcid: 3422549
doi: 10.1038/nri3073
Busada, J. T. et al. Glucocorticoids and androgens protect from gastric metaplasia by suppressing Group 2 Innate lymphoid cell activation. Gastroenterology 161, 637–652.e634 (2021).
pubmed: 33971182
doi: 10.1053/j.gastro.2021.04.075
Meyer, A. R. et al. Group 2 innate lymphoid cells coordinate damage response in the stomach. Gastroenterology 159, 2077–2091.e2078 (2020).
pubmed: 32891625
doi: 10.1053/j.gastro.2020.08.051
Petersen, C. P. et al. A signalling cascade of IL-33 to IL-13 regulates metaplasia in the mouse stomach. Gut 67, 805–817 (2018).
pubmed: 28196875
doi: 10.1136/gutjnl-2016-312779
Li, X. et al. Single-cell RNA sequencing reveals a pro-invasive cancer-associated fibroblast subgroup associated with poor clinical outcomes in patients with gastric cancer. Theranostics 12, 620–638 (2022).
pubmed: 34976204
pmcid: 8692898
doi: 10.7150/thno.60540
Chen, X. et al. Interplay of Helicobacter pylori, fibroblasts, and cancer cells induces fibroblast activation and serpin E1 expression by cancer cells to promote gastric tumorigenesis. J. Transl. Med. 20, 322 (2022).
pubmed: 35864535
pmcid: 9306099
doi: 10.1186/s12967-022-03537-x
Zhang, J. et al. Cancer-associated fibroblasts promote the migration and invasion of gastric cancer cells via activating IL-17a/JAK2/STAT3 signaling. Ann. Transl. Med. 8, 877 (2020).
pubmed: 32793721
pmcid: 7396760
doi: 10.21037/atm-20-4843
Biffi, G. & Tuveson, D. A. Diversity and biology of cancer-associated fibroblasts. Physiol. Rev. 101, 147–176 (2021).
pubmed: 32466724
doi: 10.1152/physrev.00048.2019
Plikus, M. V. et al. Fibroblasts: origins, definitions, and functions in health and disease. Cell 184, 3852–3872 (2021).
pubmed: 34297930
pmcid: 8566693
doi: 10.1016/j.cell.2021.06.024
Bu, L. et al. Biological heterogeneity and versatility of cancer-associated fibroblasts in the tumor microenvironment. Oncogene 38, 4887–4901 (2019).
pubmed: 30816343
doi: 10.1038/s41388-019-0765-y
Leedham, S. J., Brittan, M., Preston, S. L., McDonald, S. A. & Wright, N. A. The stomach periglandular fibroblast sheath: all present and correct. Gut 55, 295–296 (2006).
pubmed: 16407391
pmcid: 1856511
Direkze, N. C. et al. Multiple organ engraftment by bone-marrow-derived myofibroblasts and fibroblasts in bone-marrow-transplanted mice. Stem Cells 21, 514–520 (2003).
pubmed: 12968105
doi: 10.1634/stemcells.21-5-514
Weber, C. E. et al. Osteopontin mediates an MZF1-TGF-beta1-dependent transformation of mesenchymal stem cells into cancer-associated fibroblasts in breast cancer. Oncogene 34, 4821–4833 (2015).
pubmed: 25531323
doi: 10.1038/onc.2014.410
Quante, M. et al. Bone marrow-derived myofibroblasts contribute to the mesenchymal stem cell niche and promote tumor growth. Cancer Cell 19, 257–272 (2011).
pubmed: 21316604
pmcid: 3060401
doi: 10.1016/j.ccr.2011.01.020
LeBleu, V. S. & Neilson, E. G. Origin and functional heterogeneity of fibroblasts. FASEB J. 34, 3519–3536 (2020).
pubmed: 32037627
doi: 10.1096/fj.201903188R
Rhim, A. D. et al. Stromal elements act to restrain, rather than support, pancreatic ductal adenocarcinoma. Cancer Cell 25, 735–747 (2014).
pubmed: 24856585
pmcid: 4096698
doi: 10.1016/j.ccr.2014.04.021
Ozdemir, B. C. et al. Depletion of carcinoma-associated fibroblasts and fibrosis induces immunosuppression and accelerates pancreas cancer with reduced survival. Cancer Cell 25, 719–734 (2014).
pubmed: 24856586
pmcid: 4180632
doi: 10.1016/j.ccr.2014.04.005
Gabbiani, G., Ryan, G. B. & Majne, G. Presence of modified fibroblasts in granulation tissue and their possible role in wound contraction. Experientia 27, 549–550 (1971).
pubmed: 5132594
doi: 10.1007/BF02147594
Lendahl, U., Muhl, L. & Betsholtz, C. Identification, discrimination and heterogeneity of fibroblasts. Nat. Commun. 13, 3409 (2022).
pubmed: 35701396
pmcid: 9192344
doi: 10.1038/s41467-022-30633-9
Ohlund, D. et al. Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer. J. Exp. Med. 214, 579–596 (2017).
pubmed: 28232471
pmcid: 5339682
doi: 10.1084/jem.20162024
Galie, M. et al. Mammary carcinoma provides highly tumourigenic and invasive reactive stromal cells. Carcinogenesis 26, 1868–1878 (2005).
pubmed: 15975963
doi: 10.1093/carcin/bgi158
Kojima, Y. et al. Autocrine TGF-beta and stromal cell-derived factor-1 (SDF-1) signaling drives the evolution of tumor-promoting mammary stromal myofibroblasts. Proc. Natl Acad. Sci. USA 107, 20009–20014 (2010).
pubmed: 21041659
pmcid: 2993333
doi: 10.1073/pnas.1013805107
Guerrero-Juarez, C. F. et al. Single-cell analysis reveals fibroblast heterogeneity and myeloid-derived adipocyte progenitors in murine skin wounds. Nat. Commun. 10, 650 (2019).
pubmed: 30737373
pmcid: 6368572
doi: 10.1038/s41467-018-08247-x
Jotzu, C. et al. Adipose tissue-derived stem cells differentiate into carcinoma-associated fibroblast-like cells under the influence of tumor-derived factors. Anal. Cell Pathol. 33, 61–79 (2010).
doi: 10.1155/2010/695162
Mao, X. et al. Crosstalk between cancer-associated fibroblasts and immune cells in the tumor microenvironment: new findings and future perspectives. Mol. Cancer 20, 131 (2021).
pubmed: 34635121
pmcid: 8504100
doi: 10.1186/s12943-021-01428-1
Biffi, G. et al. IL1-Induced JAK/STAT signaling is antagonized by TGFbeta to shape CAF heterogeneity in pancreatic ductal adenocarcinoma. Cancer Discov. 9, 282–301 (2019).
pubmed: 30366930
doi: 10.1158/2159-8290.CD-18-0710
Sahai, E. et al. A framework for advancing our understanding of cancer-associated fibroblasts. Nat. Rev. Cancer 20, 174–186 (2020).
pubmed: 31980749
pmcid: 7046529
doi: 10.1038/s41568-019-0238-1
Monteran, L. & Erez, N. The dark side of fibroblasts: cancer-associated fibroblasts as mediators of immunosuppression in the tumor microenvironment. Front. Immunol. 10, 1835 (2019).
pubmed: 31428105
pmcid: 6688105
doi: 10.3389/fimmu.2019.01835
Helms, E. J. et al. Mesenchymal lineage heterogeneity underlies nonredundant functions of pancreatic cancer-associated fibroblasts. Cancer Discov. 12, 484–501 (2022).
pubmed: 34548310
doi: 10.1158/2159-8290.CD-21-0601
Elyada, E. et al. Cross-species single-cell analysis of pancreatic ductal adenocarcinoma reveals antigen-presenting cancer-associated fibroblasts. Cancer Discov. 9, 1102–1123 (2019).
pubmed: 31197017
pmcid: 6727976
doi: 10.1158/2159-8290.CD-19-0094
Utani, A., Nomizu, M. & Yamada, Y. Fibulin-2 binds to the short arms of laminin-5 and laminin-1 via conserved amino acid sequences. J. Biol. Chem. 272, 2814–2820 (1997).
pubmed: 9006922
doi: 10.1074/jbc.272.5.2814
Costa, A. et al. Fibroblast heterogeneity and immunosuppressive environment in human breast cancer. Cancer Cell 33, 463–479.e410 (2018).
pubmed: 29455927
doi: 10.1016/j.ccell.2018.01.011
Pelon, F. et al. Cancer-associated fibroblast heterogeneity in axillary lymph nodes drives metastases in breast cancer through complementary mechanisms. Nat. Commun. 11, 404 (2020).
pubmed: 31964880
pmcid: 6972713
doi: 10.1038/s41467-019-14134-w
Sebastian, A. et al. Single-cell transcriptomic analysis of tumor-derived fibroblasts and normal tissue-resident fibroblasts reveals fibroblast heterogeneity in breast cancer. Cancers 12, 1307 (2020).
pubmed: 32455670
pmcid: 7281266
doi: 10.3390/cancers12051307
Kumar, V. et al. Single-cell Atlas of Lineage States, tumor microenvironment, and subtype-specific expression programs in gastric cancer. Cancer Discov. 12, 670–691 (2022).
pubmed: 34642171
pmcid: 9394383
doi: 10.1158/2159-8290.CD-21-0683
Nowicki-Osuch, K. et al. Single-cell RNA sequencing unifies developmental programs of esophageal and gastric intestinal metaplasia. Cancer Discov. 13, 1346–1363 (2023).
pubmed: 36929873
pmcid: 10236154
doi: 10.1158/2159-8290.CD-22-0824
Zhang, Y., Cong, X., Li, Z. & Xue, Y. Estrogen facilitates gastric cancer cell proliferation and invasion through promoting the secretion of interleukin-6 by cancer-associated fibroblasts. Int. Immunopharmacol. 78, 105937 (2020).
pubmed: 31753587
doi: 10.1016/j.intimp.2019.105937
Zhu, L. et al. Crosstalk between bone marrow-derived myofibroblasts and gastric cancer cells regulates cancer stemness and promotes tumorigenesis. Oncogene 35, 5388–5399 (2016).
pubmed: 27109105
pmcid: 5063653
doi: 10.1038/onc.2016.76
Kasashima, H. et al. Lysyl oxidase-like 2 (LOXL2) from stromal fibroblasts stimulates the progression of gastric cancer. Cancer Lett. 354, 438–446 (2014).
pubmed: 25128648
doi: 10.1016/j.canlet.2014.08.014
Wu, X. et al. Hepatocyte growth factor activates tumor stromal fibroblasts to promote tumorigenesis in gastric cancer. Cancer Lett. 335, 128–135 (2013).
pubmed: 23402812
doi: 10.1016/j.canlet.2013.02.002
Zhou, Q. et al. The reciprocal interaction between tumor cells and activated fibroblasts mediated by TNF-alpha/IL-33/ST2L signaling promotes gastric cancer metastasis. Oncogene 39, 1414–1428 (2020).
pubmed: 31659258
doi: 10.1038/s41388-019-1078-x
Comito, G. et al. Cancer-associated fibroblasts and M2-polarized macrophages synergize during prostate carcinoma progression. Oncogene 33, 2423–2431 (2014).
pubmed: 23728338
doi: 10.1038/onc.2013.191
Kim, J. H. et al. The role of myofibroblasts in upregulation of S100A8 and S100A9 and the differentiation of myeloid cells in the colorectal cancer microenvironment. Biochem. Biophys. Res. Commun. 423, 60–66 (2012).
pubmed: 22634002
doi: 10.1016/j.bbrc.2012.05.081
Zhang, A. et al. Cancer-associated fibroblasts promote M2 polarization of macrophages in pancreatic ductal adenocarcinoma. Cancer Med. 6, 463–470 (2017).
pubmed: 28097809
pmcid: 5313646
doi: 10.1002/cam4.993
Izumi, D. et al. CXCL12/CXCR4 activation by cancer-associated fibroblasts promotes integrin beta1 clustering and invasiveness in gastric cancer. Int. J. Cancer 138, 1207–1219 (2016).
pubmed: 26414794
doi: 10.1002/ijc.29864
Pinchuk, I. V. et al. PD-1 ligand expression by human colonic myofibroblasts/fibroblasts regulates CD4+ T-cell activity. Gastroenterology 135, 1228–1237 (2008).
pubmed: 18760278
doi: 10.1053/j.gastro.2008.07.016
Feig, C. et al. Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes with anti-PD-L1 immunotherapy in pancreatic cancer. Proc. Natl Acad. Sci. USA 110, 20212–20217 (2013).
pubmed: 24277834
pmcid: 3864274
doi: 10.1073/pnas.1320318110
Nazareth, M. R. et al. Characterization of human lung tumor-associated fibroblasts and their ability to modulate the activation of tumor-associated T cells. J. Immunol. 178, 5552–5562 (2007).
pubmed: 17442937
doi: 10.4049/jimmunol.178.9.5552
Richards, K. E. et al. Cancer-associated fibroblast exosomes regulate survival and proliferation of pancreatic cancer cells. Oncogene 36, 1770–1778 (2017).
pubmed: 27669441
doi: 10.1038/onc.2016.353
Grunberg, N. et al. Cancer-associated fibroblasts promote aggressive gastric cancer phenotypes via heat Shock Factor 1-mediated secretion of extracellular vesicles. Cancer Res. 81, 1639–1653 (2021).
pubmed: 33547159
pmcid: 8337092
doi: 10.1158/0008-5472.CAN-20-2756
Uchihara, T. et al. Extracellular vesicles from cancer-associated fibroblasts containing Annexin A6 induces FAK-YAP activation by stabilizing beta1 integrin, enhancing drug resistance. Cancer Res. 80, 3222–3235 (2020).
pubmed: 32605995
doi: 10.1158/0008-5472.CAN-19-3803
Pitarresi, J. R. et al. Stromal ETS2 regulates chemokine production and immune cell recruitment during Acinar-to-Ductal Metaplasia. Neoplasia 18, 541–552 (2016).
pubmed: 27659014
pmcid: 5031867
doi: 10.1016/j.neo.2016.07.006
Behrens, P., Rothe, M., Wellmann, A., Krischler, J. & Wernert, N. The Ets-1 transcription factor is up-regulated together with MMP 1 and MMP 9 in the stroma of pre-invasive breast cancer. J. Pathol. 194, 43–50 (2001).
pubmed: 11329140
doi: 10.1002/path.844
Behrens, P. et al. Stromal expression of invasion-promoting, matrix-degrading proteases MMP-1 and -9 and the Ets 1 transcription factor in HNPCC carcinomas and sporadic colorectal cancers. Int. J. Cancer 107, 183–188 (2003).
pubmed: 12949792
doi: 10.1002/ijc.11336
Roy, S. A. B. et al. Loss of mesenchymal bone morphogenetic protein signaling leads to development of reactive stroma and initiation of the gastric neoplastic cascade. Sci. Rep. 6, 32759 (2016).
pubmed: 27609464
pmcid: 5016723
doi: 10.1038/srep32759
Shinohara, M. et al. Bone morphogenetic protein signaling regulates gastric epithelial cell development and proliferation in mice. Gastroenterology 139, 2050–2060.e2052 (2010).
pubmed: 20826155
doi: 10.1053/j.gastro.2010.08.052
Takabayashi, H. et al. Anti-inflammatory activity of bone morphogenetic protein signaling pathways in stomachs of mice. Gastroenterology 147, 396–406.e397 (2014).
pubmed: 24751878
doi: 10.1053/j.gastro.2014.04.015
Kapalczynska, M. et al. BMP feed-forward loop promotes terminal differentiation in gastric glands and is interrupted by H. pylori-driven inflammation. Nat. Commun. 13, 1577 (2022).
pubmed: 35332152
pmcid: 8948225
doi: 10.1038/s41467-022-29176-w
Hutton, C. et al. Single-cell analysis defines a pancreatic fibroblast lineage that supports anti-tumor immunity. Cancer Cell 39, 1227–1244.e1220 (2021).
pubmed: 34297917
pmcid: 8443274
doi: 10.1016/j.ccell.2021.06.017
Hwang, Y. J. et al. Reversibility of atrophic gastritis and intestinal metaplasia after Helicobacter pylori eradication - a prospective study for up to 10 years. Aliment Pharm. Ther. 47, 380–390 (2018).
doi: 10.1111/apt.14424
Wang, J. et al. Gastric atrophy and intestinal metaplasia before and after Helicobacter pylori eradication: a meta-analysis. Digestion 83, 253–260 (2011).
pubmed: 21282951
doi: 10.1159/000280318
Loeffler, M., Kruger, J. A., Niethammer, A. G. & Reisfeld, R. A. Targeting tumor-associated fibroblasts improves cancer chemotherapy by increasing intratumoral drug uptake. J. Clin. Investig. 116, 1955–1962 (2006).
pubmed: 16794736
pmcid: 1481657
doi: 10.1172/JCI26532
Lo, A. et al. Tumor-promoting desmoplasia is disrupted by depleting FAP-expressing stromal cells. Cancer Res. 75, 2800–2810 (2015).
pubmed: 25979873
pmcid: 4506263
doi: 10.1158/0008-5472.CAN-14-3041
Dorst, D. N. et al. Fibroblast activation protein-targeted photodynamic therapy of cancer-associated fibroblasts in murine models for pancreatic ductal adenocarcinoma. Mol. Pharm. 20, 4319–4330 (2023).
pubmed: 37485886
pmcid: 10410663
doi: 10.1021/acs.molpharmaceut.3c00453
Huang, T. X. et al. Targeting cancer-associated fibroblast-secreted WNT2 restores dendritic cell-mediated antitumour immunity. Gut 71, 333–344 (2022).
pubmed: 33692094
doi: 10.1136/gutjnl-2020-322924
Akiyama, T. et al. Stromal reprogramming through dual PDGFRalpha/beta blockade boosts the efficacy of Anti-PD-1 Immunotherapy in fibrotic tumors. Cancer Res. 83, 753–770 (2023).
pubmed: 36543251
doi: 10.1158/0008-5472.CAN-22-1890
Sherman, M. H. et al. Vitamin D receptor-mediated stromal reprogramming suppresses pancreatitis and enhances pancreatic cancer therapy. Cell 159, 80–93 (2014).
pubmed: 25259922
pmcid: 4177038
doi: 10.1016/j.cell.2014.08.007