{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,2]],"date-time":"2026-08-02T04:47:17Z","timestamp":1785646037161,"version":"3.56.0"},"reference-count":101,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01 CA255618 (ROD)"],"award-info":[{"award-number":["R01 CA255618 (ROD)"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["NIH P30CA036727 (ROD)"],"award-info":[{"award-number":["NIH P30CA036727 (ROD)"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100020496","name":"Nebraska Center for the Prevention of Obesity Diseases","doi-asserted-by":"crossref","award":["P20 GM104320 (ROD)"],"award-info":[{"award-number":["P20 GM104320 (ROD)"]}],"id":[{"id":"10.13039\/100020496","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Obesity is associated with chronic adipose dysfunction characterized by oxidative stress, inflammation, senescence, and fibrosis, which can promote tumor progression. In prostate cancer, periprostatic adipose tissue may directly influence the prostate microenvironment. Radiation therapy is widely used in prostate cancer, but radiation-induced adipose dysfunction in obesity and its impact on the prostate microenvironment remain poorly understood. In the present study, we investigated the impact of obese and irradiated obese adipose microenvironments on prostate stromal remodeling, as well as the activation of prostate fibroblasts mediating prostate cancer progression. We utilized a high-fat diet obesity model with localized adipose irradiation in animal and in vitro studies using obese and irradiated obese adipocytes. Prostates from obese and irradiated obese mice exhibited epithelial hyperplasia, increased stromal activation markers, oxidative damage, and senescence. Interestingly, radiation maintained the obesity-induced pathological behavior in the prostate, rather than elevating it. The conditioned media from obese and irradiated obese adipocytes induced stromal activation markers, senescence, extracellular H2O2 production, pro-survival signaling, and inflammation. Notably, the only significant changes observed with the addition of radiation to obesity were enhancement of fibrosis-associated features and infiltration of CD4+ T cells. Functionally, prostate myofibroblasts or senescent fibroblasts promoted prostate cancer migration and induced epithelial-to-mesenchymal transition and elevated pro-tumorigenic pathways. Cytokine profiling identified elevated levels of CXCL10 and CXCL11 from myofibroblasts, and pharmacological inhibition of CXCR3 significantly reduced prostate cancer migration, implicating this signaling axis in activated fibroblast-driven tumor-promoting crosstalk. Collectively, these findings demonstrate obesity-associated adipose dysfunction reprograms the prostate microenvironment toward a pro-tumorigenic state, while radiation sustains rather than markedly amplifies these pathological changes, identifying obese adipose-stromal crosstalk and the CXCL10\/CXCL11-CXCR3 axis as potential therapeutic targets to inhibit prostate cancer progression.<\/jats:p>","DOI":"10.3390\/cells15151387","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T10:11:38Z","timestamp":1785492698000},"page":"1387","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Adipose Dysfunction Caused by Obesity and Radiation Therapy Rewires the Prostate Stroma Toward Tumor Progression"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-9740-7475","authenticated-orcid":false,"given":"Simran","family":"Takkar","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise","family":"Monga-Wells","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arpita","family":"Chatterjee","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subodh M.","family":"Lele","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0391-142X","authenticated-orcid":false,"given":"Rebecca E.","family":"Oberley-Deegan","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,31]]},"reference":[{"key":"ref_1","first-page":"395","article-title":"Current mechanisms in obesity and tumor progression","volume":"23","author":"Fosam","year":"2020","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e70494","DOI":"10.1002\/mco2.70494","article-title":"Obesity Paradox in Cancer: A Complex Interplay Between Risk and Therapeutic Outcomes","volume":"6","author":"Chen","year":"2025","journal-title":"MedComm"},{"key":"ref_3","unstructured":"WHO Consultation on Obesity, and World Health Organization (2000). Obesity: Preventing and Managing the Global Epidemic. Report of a WHO Consultation, WHO."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"39844","DOI":"10.1038\/s41598-025-23533-7","article-title":"Irradiated obese adipocytes are prone to oxidative stress, inflammation, senescence, and fibrosis","volume":"15","author":"Takkar","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2380","DOI":"10.1038\/s41598-020-59284-w","article-title":"The Adipocyte Acquires a Fibroblast-Like Transcriptional Signature in Response to a High Fat Diet","volume":"10","author":"Jones","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"de Sousa Neto, I.V., Durigan, J.L.Q., da Silva, A.S.R., and de Cassia Marqueti, R. (2022). Adipose Tissue Extracellular Matrix Remodeling in Response to Dietary Patterns and Exercise: Molecular Landscape, Mechanistic Insights, and Therapeutic Approaches. Biology, 11.","DOI":"10.3390\/biology11050765"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/S1470-2045(14)71123-4","article-title":"Global burden of cancer attributable to high body-mass index in 2012: A population-based study","volume":"16","author":"Arnold","year":"2015","journal-title":"Lancet Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1038\/s41388-026-03718-8","article-title":"Obesity and breast density enhance immune exclusion in the primary tumor microenvironment and promote breast cancer metastasis","volume":"45","author":"Williams","year":"2026","journal-title":"Oncogene"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.jval.2018.06.020","article-title":"Physical Activity and Risk of Breast Cancer: A Meta-Analysis of 38 Cohort Studies in 45 Study Reports","volume":"22","author":"Chen","year":"2019","journal-title":"Value Health"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3343","DOI":"10.1007\/s11357-024-01375-x","article-title":"Overweight and obesity significantly increase colorectal cancer risk: A meta-analysis of 66 studies revealing a 25\u201357% elevation in risk","volume":"47","author":"Ungvari","year":"2025","journal-title":"GeroScience"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Gonzalez-Gutierrez, L., Motino, O., Barriuso, D., de la Puente-Aldea, J., Alvarez-Frutos, L., Kroemer, G., Palacios-Ramirez, R., and Senovilla, L. (2024). Obesity-Associated Colorectal Cancer. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25168836"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Aurilio, G., Piva, F., Santoni, M., Cimadamore, A., Sorgentoni, G., Lopez-Beltran, A., Cheng, L., Battelli, N., Nole, F., and Montironi, R. (2019). The Role of Obesity in Renal Cell Carcinoma Patients: Clinical-Pathological Implications. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20225683"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1038\/s41585-023-00764-9","article-title":"Obesity and prostate cancer\u2014Microenvironmental roles of adipose tissue","volume":"20","author":"Saha","year":"2023","journal-title":"Nat. Rev. Urol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4270","DOI":"10.1200\/JCO.2016.67.4283","article-title":"Obesity and Cancer Mechanisms: Tumor Microenvironment and Inflammation","volume":"34","author":"Iyengar","year":"2016","journal-title":"J. Clin. Oncol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1089\/met.2015.0095","article-title":"Obesity, Oxidative Stress, Adipose Tissue Dysfunction, and the Associated Health Risks: Causes and Therapeutic Strategies","volume":"13","author":"Manna","year":"2015","journal-title":"Metab. Syndr. Relat. Disord."},{"key":"ref_16","first-page":"139239","article-title":"Adipose tissue in obesity-related inflammation and insulin resistance: Cells, cytokines, and chemokines","volume":"2013","author":"Makki","year":"2013","journal-title":"ISRN Inflamm."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Passos, G.R., Ghezzi, A.C., Antunes, E., de Oliveira, M.G., and Monica, F.Z. (2021). The Role of Periprostatic Adipose Tissue on Prostate Function in Vascular-Related Disorders. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.626155"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/S1470-2045(21)00076-0","article-title":"Chemotherapy and radiotherapy in locally advanced head and neck cancer: An individual patient data network meta-analysis","volume":"22","author":"Petit","year":"2021","journal-title":"Lancet Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1002\/acm2.12993","article-title":"Adaptive radiotherapy based on statistical process control for oropharyngeal cancer","volume":"21","author":"Wang","year":"2020","journal-title":"J. Appl. Clin. Med. Phys."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.eururo.2022.04.003","article-title":"High-dose Radiotherapy or Androgen Deprivation Therapy (HEAT) as Treatment Intensification for Localized Prostate Cancer: An Individual Patient-data Network Meta-analysis from the MARCAP Consortium","volume":"82","author":"Kishan","year":"2022","journal-title":"Eur. Urol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1016\/j.ijrobp.2022.07.014","article-title":"Radiation Therapy in Oligometastatic Prostate Cancer","volume":"114","author":"Chinniah","year":"2022","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1056\/NEJMoa2403365","article-title":"Phase 3 Trial of Stereotactic Body Radiotherapy in Localized Prostate Cancer","volume":"391","author":"Griffin","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.clon.2020.12.011","article-title":"Intensity-modulated Radiotherapy for Rectal Cancer in the UK in 2020","volume":"33","author":"Hanna","year":"2021","journal-title":"Clin. Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1038\/s43018-021-00269-7","article-title":"Radiation therapy enhances immunotherapy response in microsatellite stable colorectal and pancreatic adenocarcinoma in a phase II trial","volume":"2","author":"Parikh","year":"2021","journal-title":"Nat. Cancer"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1111\/exd.13846","article-title":"How chemotherapy and radiotherapy damage the tissue: Comparative biology lessons from feather and hair models","volume":"28","author":"Gao","year":"2019","journal-title":"Exp. Dermatol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1038\/s41392-020-0150-x","article-title":"DNA damage response signaling pathways and targets for radiotherapy sensitization in cancer","volume":"5","author":"Huang","year":"2020","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Liermann-Wooldrik, K.T., Kosmacek, E.A., McDowell, J.A., Takkar, S., Murthy, D., Singh, P.K., Schott, M.B., Ponnusamy, M.P., and Oberley-Deegan, R.E. (2025). Radiation Promotes Acute and Chronic Damage to Adipose Tissue. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26125626"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.metabol.2018.11.001","article-title":"Obesity and cancer risk: Emerging biological mechanisms and perspectives","volume":"92","author":"Avgerinos","year":"2019","journal-title":"Metabolism"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"103543","DOI":"10.1016\/j.critrevonc.2021.103543","article-title":"Obesity and prostate cancer: A narrative review","volume":"169","author":"Wilson","year":"2022","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"11149","DOI":"10.1002\/cam4.5698","article-title":"Role of tumor microenvironment in cancer progression and therapeutic strategy","volume":"12","author":"Wang","year":"2023","journal-title":"Cancer Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1038\/s41392-020-00280-x","article-title":"The updated landscape of tumor microenvironment and drug repurposing","volume":"5","author":"Jin","year":"2020","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1016\/j.ccell.2023.02.016","article-title":"The evolving tumor microenvironment: From cancer initiation to metastatic outgrowth","volume":"41","author":"Joyce","year":"2023","journal-title":"Cancer Cell"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"12616","DOI":"10.1038\/s41598-020-69352-w","article-title":"Adipocytes protect fibroblasts from radiation-induced damage by adiponectin secretion","volume":"10","author":"Kosmacek","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1038\/s12276-023-01013-0","article-title":"Cancer-associated fibroblasts: From basic science to anticancer therapy","volume":"55","author":"Yang","year":"2023","journal-title":"Exp. Mol. Med."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Joshi, R.S., Kanugula, S.S., Sudhir, S., Pereira, M.P., Jain, S., and Aghi, M.K. (2021). The Role of Cancer-Associated Fibroblasts in Tumor Progression. Cancers, 13.","DOI":"10.3390\/cancers13061399"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.cytogfr.2024.03.004","article-title":"From orphan to oncogene: The role of GPR35 in cancer and immune modulation","volume":"77","author":"Takkar","year":"2024","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1038\/s41419-021-03545-7","article-title":"Cancer-associated fibroblast-derived CXCL11 modulates hepatocellular carcinoma cell migration and tumor metastasis through the circUBAP2\/miR-4756\/IFIT1\/3 axis","volume":"12","author":"Liu","year":"2021","journal-title":"Cell Death Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"4657","DOI":"10.1038\/s41388-025-03601-y","article-title":"Cytokine CCL2 secreted by cancer-associated fibroblasts augments temozolomide resistance in glioblastoma through ERK1\/2 signaling","volume":"44","author":"Zuo","year":"2025","journal-title":"Oncogene"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1038\/s41419-022-05351-1","article-title":"Cancer-associated fibroblasts in pancreatic ductal adenocarcinoma","volume":"13","author":"Zhang","year":"2022","journal-title":"Cell Death Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1038\/s41419-025-07588-y","article-title":"FGFR4 promotes CAF activation through the CXCL10-CXCR3 axis in colon cancer","volume":"16","author":"Sun","year":"2025","journal-title":"Cell Death Dis."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"109674","DOI":"10.1016\/j.isci.2024.109674","article-title":"Cancer-associated fibroblasts promote enzalutamide resistance and PD-L1 expression in prostate cancer through CCL5-CCR5 paracrine axis","volume":"27","author":"Xiong","year":"2024","journal-title":"iScience"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1667\/RR14623.1","article-title":"MnTE-2-PyP Treatment, or NOX4 Inhibition, Protects against Radiation-Induced Damage in Mouse Primary Prostate Fibroblasts by Inhibiting the TGF-Beta 1 Signaling Pathway","volume":"187","author":"Chatterjee","year":"2017","journal-title":"Radiat. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"34532","DOI":"10.18632\/oncotarget.8923","article-title":"MnTnBuOE-2-PyP protects normal colorectal fibroblasts from radiation damage and simultaneously enhances radio\/chemotherapeutic killing of colorectal cancer cells","volume":"7","author":"Kosmacek","year":"2016","journal-title":"Oncotarget"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Mubtasim, N., and Gollahon, L. (2023). Characterizing 3T3-L1 MBX Adipocyte Cell Differentiation Maintained with Fatty Acids as an In Vitro Model to Study the Effects of Obesity. Life, 13.","DOI":"10.3390\/life13081712"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"103219","DOI":"10.1016\/j.redox.2024.103219","article-title":"Exogenous APN protects normal tissues from radiation-induced oxidative damage and fibrosis in mice and prostate cancer patients with higher levels of APN have less radiation-induced toxicities","volume":"73","author":"McDowell","year":"2024","journal-title":"Redox Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"102301","DOI":"10.1016\/j.redox.2022.102301","article-title":"MnTE-2-PyP protects fibroblast mitochondria from hyperglycemia and radiation exposure","volume":"52","author":"Chatterjee","year":"2022","journal-title":"Redox Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"101542","DOI":"10.1016\/j.redox.2020.101542","article-title":"MnTE-2-PyP, a manganese porphyrin, reduces cytotoxicity caused by irradiation in a diabetic environment through the induction of endogenous antioxidant defenses","volume":"34","author":"Chatterjee","year":"2020","journal-title":"Redox Biol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Masenga, S.K., Kabwe, L.S., Chakulya, M., and Kirabo, A. (2023). Mechanisms of Oxidative Stress in Metabolic Syndrome. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24097898"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Zhang, Z., Zhao, L., Zhou, X., Meng, X., and Zhou, X. (2022). Role of inflammation, immunity, and oxidative stress in hypertension: New insights and potential therapeutic targets. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.1098725"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Luo, J., Li, L., Shi, W., Xu, K., Shen, Y., and Dai, B. (2025). Oxidative stress and inflammation: Roles in osteoporosis. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1611932"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1038\/s41418-024-01266-w","article-title":"SLC15A3 plays a crucial role in pulmonary fibrosis by regulating macrophage oxidative stress","volume":"31","author":"Luo","year":"2024","journal-title":"Cell Death Differ."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.matbio.2017.11.010","article-title":"Inflammation and fibrosis","volume":"68\u201369","author":"Mack","year":"2018","journal-title":"Matrix Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"C375","DOI":"10.1152\/ajpcell.00379.2020","article-title":"Adipose tissue inflammation and metabolic dysfunction in obesity","volume":"320","author":"Kawai","year":"2021","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Li, X., Ren, Y., Chang, K., Wu, W., Griffiths, H.R., Lu, S., and Gao, D. (2023). Adipose tissue macrophages as potential targets for obesity and metabolic diseases. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1153915"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"El Alaa, R.S.A., Al-Mannai, W., Darwish, N., and Al-Mansoori, L. (2024). Adipose-Derived Stromal Cells and Cancer-Associated Fibroblasts: Interactions and Implications in Tumor Progression. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms252111558"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1007\/s10555-024-10186-7","article-title":"Cancer-associated fibroblasts: A versatile mediator in tumor progression, metastasis, and targeted therapy","volume":"43","author":"Guo","year":"2024","journal-title":"Cancer Metastasis Rev."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1038\/s41420-025-02566-x","article-title":"Cancer-associated fibroblasts in cancer drug resistance and cancer progression: A review","volume":"11","author":"Masuda","year":"2025","journal-title":"Cell Death Discov."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1111\/cas.16418","article-title":"Cancer-associated fibroblast-derived MMP11 promotes tumor progression in pancreatic cancer","volume":"116","author":"Wang","year":"2025","journal-title":"Cancer Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3014","DOI":"10.7150\/thno.94207","article-title":"Cancer-associated fibroblast-derived periostin promotes papillary thyroid tumor growth through integrin-FAK-STAT3 signaling","volume":"14","author":"Jin","year":"2024","journal-title":"Theranostics"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1186\/s13046-020-01611-0","article-title":"Regulation of heterogeneous cancer-associated fibroblasts: The molecular pathology of activated signaling pathways","volume":"39","author":"Yoshida","year":"2020","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1186\/s13046-023-02900-0","article-title":"Cancer-associated fibroblasts-derived CXCL12 enhances immune escape of bladder cancer through inhibiting P62-mediated autophagic degradation of PDL1","volume":"42","author":"Zhang","year":"2023","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"10286","DOI":"10.1038\/s41598-020-67175-3","article-title":"Human Adipocyte Conditioned Medium Promotes In Vitro Fibroblast Conversion to Myofibroblasts","volume":"10","author":"Nagumo","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1186\/s43556-025-00360-w","article-title":"Fibroblasts promote the progression of benign prostatic hyperplasia through colony-stimulating factor 1 receptor-mediated RTK signaling in prostatic epithelial cells","volume":"6","author":"Zhan","year":"2025","journal-title":"Mol. Biomed."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1038\/s41419-023-06240-x","article-title":"Crosstalk with lung fibroblasts shapes the growth and therapeutic response of mesothelioma cells","volume":"14","author":"Chrisochoidou","year":"2023","journal-title":"Cell Death Dis."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1590","DOI":"10.1093\/rpd\/ncae027","article-title":"Mitochondrial reactive oxygen species-mediated fibroblast activation has a role in tumor microenvironment formation in radiation carcinogenesis","volume":"200","author":"Shimura","year":"2024","journal-title":"Radiat. Prot. Dosim."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"104745","DOI":"10.1016\/j.phrs.2020.104745","article-title":"TGF-beta in radiotherapy: Mechanisms of tumor resistance and normal tissues injury","volume":"155","author":"Farhood","year":"2020","journal-title":"Pharmacol. Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.semcancer.2020.05.001","article-title":"Melanoma in the liver: Oxidative stress and the mechanisms of metastatic cell survival","volume":"71","author":"Obrador","year":"2021","journal-title":"Semin. Cancer Biol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"109670","DOI":"10.1016\/j.cellsig.2020.109670","article-title":"Oxidative stress responsive transcription factors in cellular signalling transduction mechanisms","volume":"72","author":"Vishnupriya","year":"2020","journal-title":"Cell. Signal."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.1038\/s12276-025-01480-7","article-title":"Hallmarks of cellular senescence: Biology, mechanisms, regulations","volume":"57","author":"Ajoolabady","year":"2025","journal-title":"Exp. Mol. Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1186\/s12943-025-02284-z","article-title":"Regulation of cellular senescence in tumor progression and therapeutic targeting: Mechanisms and pathways","volume":"24","author":"Liu","year":"2025","journal-title":"Mol. Cancer"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1038\/s41580-024-00727-x","article-title":"The senescence-associated secretory phenotype and its physiological and pathological implications","volume":"25","author":"Wang","year":"2024","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.2337\/db21-0536","article-title":"Diabetes-Induced Cellular Senescence and Senescence-Associated Secretory Phenotype Impair Cardiac Regeneration and Function Independently of Age","volume":"71","author":"Marino","year":"2022","journal-title":"Diabetes"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1038\/ncb1909","article-title":"Persistent DNA damage signalling triggers senescence-associated inflammatory cytokine secretion","volume":"11","author":"Rodier","year":"2009","journal-title":"Nat. Cell Biol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"104020","DOI":"10.1016\/j.redox.2026.104020","article-title":"BMX-001, a clinically relevant radioprotector, can reverse radiation-induced fibrosis when given three weeks after radiation, in part, by restoring methylation","volume":"90","author":"Myers","year":"2026","journal-title":"Redox Biol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"3333","DOI":"10.1002\/1878-0261.13268","article-title":"Cellular senescence and the tumour microenvironment","volume":"16","author":"Takasugi","year":"2022","journal-title":"Mol. Oncol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.canlet.2020.06.019","article-title":"Endothelial cells under therapy-induced senescence secrete CXCL11, which increases aggressiveness of breast cancer cells","volume":"490","author":"Hwang","year":"2020","journal-title":"Cancer Lett."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1016\/j.semcancer.2021.11.004","article-title":"Tumor microenvironment and cellular senescence: Understanding therapeutic resistance and harnessing strategies","volume":"86","author":"Liu","year":"2022","journal-title":"Semin. Cancer Biol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"H303","DOI":"10.1152\/ajpheart.00545.2023","article-title":"Fibroblasts and immune cells: At the crossroad of organ inflammation and fibrosis","volume":"326","author":"Smolgovsky","year":"2024","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1038\/s41590-021-00927-z","article-title":"Hallmarks of T cell aging","volume":"22","author":"Mittelbrunn","year":"2021","journal-title":"Nat. Immunol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1158\/2159-8290.CD-15-1177","article-title":"Obesity-Induced Inflammation and Desmoplasia Promote Pancreatic Cancer Progression and Resistance to Chemotherapy","volume":"6","author":"Incio","year":"2016","journal-title":"Cancer Discov."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Zhou, Y., Zhang, H., Yao, Y., Zhang, X., Guan, Y., and Zheng, F. (2022). CD4(+) T cell activation and inflammation in NASH-related fibrosis. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.967410"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1016\/j.jcmgh.2022.12.005","article-title":"Fibroblast Activation Protein Activates Macrophages and Promotes Parenchymal Liver Inflammation and Fibrosis","volume":"15","author":"Yang","year":"2023","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"S22","DOI":"10.1038\/ki.2010.418","article-title":"Mechanistic connection between inflammation and fibrosis","volume":"78","author":"Lee","year":"2010","journal-title":"Kidney Int."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.ccell.2023.12.002","article-title":"EGFR-activated myofibroblasts promote metastasis of pancreatic cancer","volume":"42","author":"Mucciolo","year":"2024","journal-title":"Cancer Cell"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"103209","DOI":"10.1016\/j.redox.2024.103209","article-title":"Lactate-induced activation of tumor-associated fibroblasts and IL-8-mediated macrophage recruitment promote lung cancer progression","volume":"74","author":"Gu","year":"2024","journal-title":"Redox Biol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"3653","DOI":"10.1038\/s41467-025-58748-9","article-title":"Hypoxia-induced Wnt5a-secreting fibroblasts promote colon cancer progression","volume":"16","author":"Harada","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"e26852","DOI":"10.1016\/j.heliyon.2024.e26852","article-title":"TREM1 promotes cancer associated malignant phenotype through activated MAPK signaling pathway and predicts poor prognosis in gastric cancer","volume":"10","author":"Chen","year":"2024","journal-title":"Heliyon"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"61183","DOI":"10.18632\/oncotarget.11282","article-title":"IL-13\/STAT6 signaling plays a critical role in the epithelial-mesenchymal transition of colorectal cancer cells","volume":"7","author":"Cao","year":"2016","journal-title":"Oncotarget"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"188802","DOI":"10.1016\/j.bbcan.2022.188802","article-title":"Interleukin 13 receptor alpha 2 (IL13Ralpha2): Expression, signaling pathways and therapeutic applications in cancer","volume":"1877","author":"Jaen","year":"2022","journal-title":"Biochim. Biophys. Acta Rev. Cancer."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1007\/s12264-020-00608-1","article-title":"CXCL10\/CXCR3 Signaling in the DRG Exacerbates Neuropathic Pain in Mice","volume":"37","author":"Kong","year":"2021","journal-title":"Neurosci. Bull."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"104320","DOI":"10.1016\/j.jpet.2026.104320","article-title":"SOX11-mediated CXCL10\/CXCR3 activation promotes neuroendocrine prostate cancer","volume":"393","author":"Ding","year":"2026","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"2306","DOI":"10.1007\/s12094-023-03126-4","article-title":"Targeting CXCL9\/10\/11-CXCR3 axis: An important component of tumor-promoting and antitumor immunity","volume":"25","author":"Pan","year":"2023","journal-title":"Clin. Transl. Oncol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1016\/j.ajpath.2019.12.004","article-title":"CXCL11-CXCR3 Axis Mediates Tumor Lymphatic Cross Talk and Inflammation-Induced Tumor, Promoting Pathways in Head and Neck Cancers","volume":"190","author":"Kumaravel","year":"2020","journal-title":"Am. J. Pathol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.canlet.2021.03.002","article-title":"Interferon regulatory factor 1(IRF-1) activates anti-tumor immunity via CXCL10\/CXCR3 axis in hepatocellular carcinoma (HCC)","volume":"506","author":"Yan","year":"2021","journal-title":"Cancer Lett."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Pati, S., Irfan, W., Jameel, A., Ahmed, S., and Shahid, R.K. (2023). Obesity and Cancer: A Current Overview of Epidemiology, Pathogenesis, Outcomes, and Management. Cancers, 15.","DOI":"10.3390\/cancers15020485"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1038\/s41416-019-0509-3","article-title":"Cancer-associated fibroblasts-heroes or villains?","volume":"121","author":"Gieniec","year":"2019","journal-title":"Br. J. Cancer"},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Lan, X., Li, W., Zhao, K., Wang, J., Li, S., and Zhao, H. (2025). Revisiting the role of cancer-associated fibroblasts in tumor microenvironment. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1582532"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1186\/s12967-025-06744-4","article-title":"Paracrine signaling in cancer-associated fibroblasts: Central regulators of the tumor immune microenvironment","volume":"23","author":"Li","year":"2025","journal-title":"J. Transl. Med."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"e2423130122","DOI":"10.1073\/pnas.2423130122","article-title":"The FBXW7-KMT2 axis in cancer-associated fibroblasts controls tumor growth via an epigenetic-paracrine mechanism","volume":"122","author":"Yin","year":"2025","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"e2320513","DOI":"10.1001\/jamanetworkopen.2023.20513","article-title":"Association of Body Mass Index with Outcomes Among Patients with Head and Neck Cancer Treated with Chemoradiotherapy","volume":"6","author":"Ma","year":"2023","journal-title":"JAMA Netw. Open"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1038\/s41574-024-01032-5","article-title":"The multifactorial effect of obesity on the effectiveness and outcomes of cancer therapies","volume":"20","author":"Lysaght","year":"2024","journal-title":"Nat. Rev. Endocrinol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/15\/1387\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,2]],"date-time":"2026-08-02T04:23:55Z","timestamp":1785644635000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/15\/1387"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,31]]},"references-count":101,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["cells15151387"],"URL":"https:\/\/doi.org\/10.3390\/cells15151387","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,31]]}}}