Thyroid Hormone Activation Regulates the Crosstalk between Breast Cancer and Mesenchymal Stem Cells
Background: Thyroid Hormones (THs) critically impact human cancer. Although endowed with both tumor-promoting and inhibiting effects in different cancer types, excess of THs has been linked to enhanced tumor growth and progression. Breast cancer depends on the interaction between...
Saved in:
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
IMR Press
2025-01-01
|
| Series: | Frontiers in Bioscience-Landmark |
| Subjects: | |
| Online Access: | https://www.imrpress.com/journal/FBL/30/1/10.31083/FBL26113 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832586536511602688 |
|---|---|
| author | Annarita Nappi Vittoria D’Esposito Caterina Miro Alessia Parascandolo Annunziata Gaetana Cicatiello Serena Sagliocchi Lucia Acampora Sepehr Torabinejad Federica Restolfer Maddalena Raia Melania Murolo Emery Di Cicco Pietro Formisano Monica Dentice |
| author_facet | Annarita Nappi Vittoria D’Esposito Caterina Miro Alessia Parascandolo Annunziata Gaetana Cicatiello Serena Sagliocchi Lucia Acampora Sepehr Torabinejad Federica Restolfer Maddalena Raia Melania Murolo Emery Di Cicco Pietro Formisano Monica Dentice |
| author_sort | Annarita Nappi |
| collection | DOAJ |
| description | Background: Thyroid Hormones (THs) critically impact human cancer. Although endowed with both tumor-promoting and inhibiting effects in different cancer types, excess of THs has been linked to enhanced tumor growth and progression. Breast cancer depends on the interaction between bulk tumor cells and the surrounding microenvironment in which mesenchymal stem cells (MSCs) exert powerful pro-tumorigenic activities. Methods: Primary human MSCs from healthy female donors were co-cultured with DIO2 knock out (D2KO) and wild type (WT) MCF7 breast cancer cells to assess cell growth, migration, invasion and the expression of known epithelial-mesenchymal transition (EMT)- and inflammation-related markers. Furthermore, a surgery-free intraductal delivery model, i.e., the Mouse-INtraDuctal (MIND) injection method, was used as a tool for in vivo characterization of breast tumor formation and progression. Results: In this study, we uncovered a novel role of THs in regulating the tumor-stroma crosstalk. MCF7 cells enhanced the intracellular activation of THs through the TH-activating enzyme, D2, fostering their EMT properties and the dialogue with MSCs. D2 inactivation reduced the invasiveness of MCF7 cells and their responsiveness to the pro-tumorigenic induction via MSCs, both in vivo and in vitro. Conclusions: Thus, we argue that intracellular activation of THs via D2 is a critical requirement for invasive and metastatic conversion of breast cancer cells, advising the blocking of D2 as a potential therapeutic tool for cancer therapy. |
| format | Article |
| id | doaj-art-cd244c3e446749a7b718313f6efb3bd5 |
| institution | Kabale University |
| issn | 2768-6701 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | IMR Press |
| record_format | Article |
| series | Frontiers in Bioscience-Landmark |
| spelling | doaj-art-cd244c3e446749a7b718313f6efb3bd52025-01-25T08:55:52ZengIMR PressFrontiers in Bioscience-Landmark2768-67012025-01-013012611310.31083/FBL26113S2768-6701(24)01588-0Thyroid Hormone Activation Regulates the Crosstalk between Breast Cancer and Mesenchymal Stem CellsAnnarita Nappi0Vittoria D’Esposito1Caterina Miro2Alessia Parascandolo3Annunziata Gaetana Cicatiello4Serena Sagliocchi5Lucia Acampora6Sepehr Torabinejad7Federica Restolfer8Maddalena Raia9Melania Murolo10Emery Di Cicco11Pietro Formisano12Monica Dentice13Department of Clinical Medicine and Surgery, University of Naples “Federico II”, 80131 Naples, ItalyDepartment of Translational Medicine, University of Naples “Federico II”, 80131 Naples, ItalyDepartment of Clinical Medicine and Surgery, University of Naples “Federico II”, 80131 Naples, ItalyDepartment of Translational Medicine, University of Naples “Federico II”, 80131 Naples, ItalyDepartment of Clinical Medicine and Surgery, University of Naples “Federico II”, 80131 Naples, ItalyDepartment of Clinical Medicine and Surgery, University of Naples “Federico II”, 80131 Naples, ItalyDepartment of Clinical Medicine and Surgery, University of Naples “Federico II”, 80131 Naples, ItalyDepartment of Clinical Medicine and Surgery, University of Naples “Federico II”, 80131 Naples, ItalyDepartment of Clinical Medicine and Surgery, University of Naples “Federico II”, 80131 Naples, ItalyCEINGE – Biotecnologie Avanzate Società consortile a responsabilità limitata (S.c.a.r.l.), 80131 Naples, ItalyDepartment of Clinical Medicine and Surgery, University of Naples “Federico II”, 80131 Naples, ItalyDepartment of Clinical Medicine and Surgery, University of Naples “Federico II”, 80131 Naples, ItalyDepartment of Translational Medicine, University of Naples “Federico II”, 80131 Naples, ItalyDepartment of Clinical Medicine and Surgery, University of Naples “Federico II”, 80131 Naples, ItalyBackground: Thyroid Hormones (THs) critically impact human cancer. Although endowed with both tumor-promoting and inhibiting effects in different cancer types, excess of THs has been linked to enhanced tumor growth and progression. Breast cancer depends on the interaction between bulk tumor cells and the surrounding microenvironment in which mesenchymal stem cells (MSCs) exert powerful pro-tumorigenic activities. Methods: Primary human MSCs from healthy female donors were co-cultured with DIO2 knock out (D2KO) and wild type (WT) MCF7 breast cancer cells to assess cell growth, migration, invasion and the expression of known epithelial-mesenchymal transition (EMT)- and inflammation-related markers. Furthermore, a surgery-free intraductal delivery model, i.e., the Mouse-INtraDuctal (MIND) injection method, was used as a tool for in vivo characterization of breast tumor formation and progression. Results: In this study, we uncovered a novel role of THs in regulating the tumor-stroma crosstalk. MCF7 cells enhanced the intracellular activation of THs through the TH-activating enzyme, D2, fostering their EMT properties and the dialogue with MSCs. D2 inactivation reduced the invasiveness of MCF7 cells and their responsiveness to the pro-tumorigenic induction via MSCs, both in vivo and in vitro. Conclusions: Thus, we argue that intracellular activation of THs via D2 is a critical requirement for invasive and metastatic conversion of breast cancer cells, advising the blocking of D2 as a potential therapeutic tool for cancer therapy.https://www.imrpress.com/journal/FBL/30/1/10.31083/FBL26113thyroid hormonesdeiodinasesbreast cancermesenchymal stem cells |
| spellingShingle | Annarita Nappi Vittoria D’Esposito Caterina Miro Alessia Parascandolo Annunziata Gaetana Cicatiello Serena Sagliocchi Lucia Acampora Sepehr Torabinejad Federica Restolfer Maddalena Raia Melania Murolo Emery Di Cicco Pietro Formisano Monica Dentice Thyroid Hormone Activation Regulates the Crosstalk between Breast Cancer and Mesenchymal Stem Cells Frontiers in Bioscience-Landmark thyroid hormones deiodinases breast cancer mesenchymal stem cells |
| title | Thyroid Hormone Activation Regulates the Crosstalk between Breast Cancer and Mesenchymal Stem Cells |
| title_full | Thyroid Hormone Activation Regulates the Crosstalk between Breast Cancer and Mesenchymal Stem Cells |
| title_fullStr | Thyroid Hormone Activation Regulates the Crosstalk between Breast Cancer and Mesenchymal Stem Cells |
| title_full_unstemmed | Thyroid Hormone Activation Regulates the Crosstalk between Breast Cancer and Mesenchymal Stem Cells |
| title_short | Thyroid Hormone Activation Regulates the Crosstalk between Breast Cancer and Mesenchymal Stem Cells |
| title_sort | thyroid hormone activation regulates the crosstalk between breast cancer and mesenchymal stem cells |
| topic | thyroid hormones deiodinases breast cancer mesenchymal stem cells |
| url | https://www.imrpress.com/journal/FBL/30/1/10.31083/FBL26113 |
| work_keys_str_mv | AT annaritanappi thyroidhormoneactivationregulatesthecrosstalkbetweenbreastcancerandmesenchymalstemcells AT vittoriadesposito thyroidhormoneactivationregulatesthecrosstalkbetweenbreastcancerandmesenchymalstemcells AT caterinamiro thyroidhormoneactivationregulatesthecrosstalkbetweenbreastcancerandmesenchymalstemcells AT alessiaparascandolo thyroidhormoneactivationregulatesthecrosstalkbetweenbreastcancerandmesenchymalstemcells AT annunziatagaetanacicatiello thyroidhormoneactivationregulatesthecrosstalkbetweenbreastcancerandmesenchymalstemcells AT serenasagliocchi thyroidhormoneactivationregulatesthecrosstalkbetweenbreastcancerandmesenchymalstemcells AT luciaacampora thyroidhormoneactivationregulatesthecrosstalkbetweenbreastcancerandmesenchymalstemcells AT sepehrtorabinejad thyroidhormoneactivationregulatesthecrosstalkbetweenbreastcancerandmesenchymalstemcells AT federicarestolfer thyroidhormoneactivationregulatesthecrosstalkbetweenbreastcancerandmesenchymalstemcells AT maddalenaraia thyroidhormoneactivationregulatesthecrosstalkbetweenbreastcancerandmesenchymalstemcells AT melaniamurolo thyroidhormoneactivationregulatesthecrosstalkbetweenbreastcancerandmesenchymalstemcells AT emerydicicco thyroidhormoneactivationregulatesthecrosstalkbetweenbreastcancerandmesenchymalstemcells AT pietroformisano thyroidhormoneactivationregulatesthecrosstalkbetweenbreastcancerandmesenchymalstemcells AT monicadentice thyroidhormoneactivationregulatesthecrosstalkbetweenbreastcancerandmesenchymalstemcells |