Interleukin-1β mediates a tumor-supporting environment prompted by IGF1 in triple-negative breast cancer (TNBC)
Abstract Background The intricate mechanisms that associate obesity with triple-negative breast cancer (TNBC) remain to be disclosed. Considering that obesity is linked with an increased bioavailability of the insulin-like growth factor 1 (IGF1), we evaluated whether IGF1 triggers aggressive feature...
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BMC
2025-06-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-025-06730-w |
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| author | Domenica Scordamaglia Marianna Talia Francesca Cirillo Azzurra Zicarelli Adelina Assunta Mondino Salvatore De Rosis Marika Di Dio Francesca Silvestri Chiara Meliti Anna Maria Miglietta Carlo Capalbo Ernestina Marianna De Francesco Antonino Belfiore Marcello Maggiolini Rosamaria Lappano |
| author_facet | Domenica Scordamaglia Marianna Talia Francesca Cirillo Azzurra Zicarelli Adelina Assunta Mondino Salvatore De Rosis Marika Di Dio Francesca Silvestri Chiara Meliti Anna Maria Miglietta Carlo Capalbo Ernestina Marianna De Francesco Antonino Belfiore Marcello Maggiolini Rosamaria Lappano |
| author_sort | Domenica Scordamaglia |
| collection | DOAJ |
| description | Abstract Background The intricate mechanisms that associate obesity with triple-negative breast cancer (TNBC) remain to be disclosed. Considering that obesity is linked with an increased bioavailability of the insulin-like growth factor 1 (IGF1), we evaluated whether IGF1 triggers aggressive features in TNBC cells and the molecular paths involved. Methods Gene expression and Chromatin Immunoprecipitation experiments, ELISA, immunoblotting, immunoprecipitation and immunofluorescence assays, combined with two-dimensional and three-dimensional in vitro model-based studies, were used to investigate the molecular mechanisms through which IGF1 may promote proliferative and motile responses in TNBC cells and reprogram normal fibroblasts into cancer-associated fibroblasts (CAFs)-like cells. The translational relevance of the results obtained was supported by bioinformatics analyses leveraging data from extensive TNBC patient databases. Results We found that the cytokine interleukin-1β (IL-1β) mediates certain IGF1 actions within the tumor microenvironment, hence facilitating the TNBC landscape. Mechanistically, we assessed that the IGF1/IGF1 receptor (IGFIR) axis induces the collagen VI-dependent activation of discoidin domain receptor 1 (DDR1) and the subsequent increase of the G protein estrogen receptor (GPER), toward IL-1β regulation and secretion. Consequently, IL-1β promoted both the autocrine stimulation of TNBC cells and the differentiation of normal fibroblasts into cancer-associated fibroblasts (CAFs)-like cells, which in turn achieved a proliferative profile and enhanced the motility of TNBC cells. Conclusions IL-1β may be considered as a therapeutic target in more comprehensive approaches in obese TNBC patients exhibiting high IGF-1 bioavailability. |
| format | Article |
| id | doaj-art-1c64e43c3a7f4145b311ce2587c85df8 |
| institution | DOAJ |
| issn | 1479-5876 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj-art-1c64e43c3a7f4145b311ce2587c85df82025-08-20T03:22:54ZengBMCJournal of Translational Medicine1479-58762025-06-0123111910.1186/s12967-025-06730-wInterleukin-1β mediates a tumor-supporting environment prompted by IGF1 in triple-negative breast cancer (TNBC)Domenica Scordamaglia0Marianna Talia1Francesca Cirillo2Azzurra Zicarelli3Adelina Assunta Mondino4Salvatore De Rosis5Marika Di Dio6Francesca Silvestri7Chiara Meliti8Anna Maria Miglietta9Carlo Capalbo10Ernestina Marianna De Francesco11Antonino Belfiore12Marcello Maggiolini13Rosamaria Lappano14Department of Pharmacy, Health and Nutritional Sciences, University of CalabriaDepartment of Pharmacy, Health and Nutritional Sciences, University of CalabriaDepartment of Medicine and Surgery, University of Enna “Kore”Department of Medicine and Surgery, University of Enna “Kore”Department of Pharmacy, Health and Nutritional Sciences, University of CalabriaDepartment of Pharmacy, Health and Nutritional Sciences, University of CalabriaDepartment of Pharmacy, Health and Nutritional Sciences, University of CalabriaDepartment of Pharmacy, Health and Nutritional Sciences, University of CalabriaDepartment of Pharmacy, Health and Nutritional Sciences, University of CalabriaBreast and General Surgery Unit, Annunziata Hospital CosenzaDepartment of Pharmacy, Health and Nutritional Sciences, University of CalabriaDepartment of Medicine and Surgery, University of Enna “Kore”Endocrinology, Department of Clinical and Experimental Medicine, University of Catania, Garibaldi-Nesima HospitalDepartment of Pharmacy, Health and Nutritional Sciences, University of CalabriaDepartment of Pharmacy, Health and Nutritional Sciences, University of CalabriaAbstract Background The intricate mechanisms that associate obesity with triple-negative breast cancer (TNBC) remain to be disclosed. Considering that obesity is linked with an increased bioavailability of the insulin-like growth factor 1 (IGF1), we evaluated whether IGF1 triggers aggressive features in TNBC cells and the molecular paths involved. Methods Gene expression and Chromatin Immunoprecipitation experiments, ELISA, immunoblotting, immunoprecipitation and immunofluorescence assays, combined with two-dimensional and three-dimensional in vitro model-based studies, were used to investigate the molecular mechanisms through which IGF1 may promote proliferative and motile responses in TNBC cells and reprogram normal fibroblasts into cancer-associated fibroblasts (CAFs)-like cells. The translational relevance of the results obtained was supported by bioinformatics analyses leveraging data from extensive TNBC patient databases. Results We found that the cytokine interleukin-1β (IL-1β) mediates certain IGF1 actions within the tumor microenvironment, hence facilitating the TNBC landscape. Mechanistically, we assessed that the IGF1/IGF1 receptor (IGFIR) axis induces the collagen VI-dependent activation of discoidin domain receptor 1 (DDR1) and the subsequent increase of the G protein estrogen receptor (GPER), toward IL-1β regulation and secretion. Consequently, IL-1β promoted both the autocrine stimulation of TNBC cells and the differentiation of normal fibroblasts into cancer-associated fibroblasts (CAFs)-like cells, which in turn achieved a proliferative profile and enhanced the motility of TNBC cells. Conclusions IL-1β may be considered as a therapeutic target in more comprehensive approaches in obese TNBC patients exhibiting high IGF-1 bioavailability.https://doi.org/10.1186/s12967-025-06730-wInterleukin 1β (IL1β)Triple-negative breast cancer (TNBC)Cancer associated fibroblasts (CAFs)Insulin-like growth factor 1 (IGF1)Discoidin domain receptor 1 (DDR1)G protein estrogen receptor (GPER) |
| spellingShingle | Domenica Scordamaglia Marianna Talia Francesca Cirillo Azzurra Zicarelli Adelina Assunta Mondino Salvatore De Rosis Marika Di Dio Francesca Silvestri Chiara Meliti Anna Maria Miglietta Carlo Capalbo Ernestina Marianna De Francesco Antonino Belfiore Marcello Maggiolini Rosamaria Lappano Interleukin-1β mediates a tumor-supporting environment prompted by IGF1 in triple-negative breast cancer (TNBC) Journal of Translational Medicine Interleukin 1β (IL1β) Triple-negative breast cancer (TNBC) Cancer associated fibroblasts (CAFs) Insulin-like growth factor 1 (IGF1) Discoidin domain receptor 1 (DDR1) G protein estrogen receptor (GPER) |
| title | Interleukin-1β mediates a tumor-supporting environment prompted by IGF1 in triple-negative breast cancer (TNBC) |
| title_full | Interleukin-1β mediates a tumor-supporting environment prompted by IGF1 in triple-negative breast cancer (TNBC) |
| title_fullStr | Interleukin-1β mediates a tumor-supporting environment prompted by IGF1 in triple-negative breast cancer (TNBC) |
| title_full_unstemmed | Interleukin-1β mediates a tumor-supporting environment prompted by IGF1 in triple-negative breast cancer (TNBC) |
| title_short | Interleukin-1β mediates a tumor-supporting environment prompted by IGF1 in triple-negative breast cancer (TNBC) |
| title_sort | interleukin 1β mediates a tumor supporting environment prompted by igf1 in triple negative breast cancer tnbc |
| topic | Interleukin 1β (IL1β) Triple-negative breast cancer (TNBC) Cancer associated fibroblasts (CAFs) Insulin-like growth factor 1 (IGF1) Discoidin domain receptor 1 (DDR1) G protein estrogen receptor (GPER) |
| url | https://doi.org/10.1186/s12967-025-06730-w |
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