Thyroid status regulates the tumor microenvironment delineating breast cancer fate
The patient's hormonal context plays a crucial role in the outcome of cancer. However, the association between thyroid disease and breast cancer risk remains unclear. We evaluated the effect of thyroid status on breast cancer growth and dissemination in an immunocompetent mouse model. For this, hyperthyroid and hypothyroid Balb/c mice were orthotopically inoculated with triple-negative breast cancer 4T1 cells. Tumors from hyperthyroid mice showed an increased growth rate and an immunosuppressive tumor microenvironment, characterized by increased IL-10 levels and decreased percentage of activated cytotoxic T cells. On the other hand, delayed tumor growth in hypothyroid animals was associated with increased tumor infiltration of activated CD8+ cells and a high IFNγ/IL-10 ratio. Paradoxically, hypothyroid mice developed a higher number of lung metastasis than hyperthyroid animals. This was related to an increased secretion of tumor CCL2 and an immunosuppressive systemic environment, with increased proportion of regulatory T cells and IL-10 levels in spleens. A lower number of lung metastasis in hyperthyroid mice was related to the reduced presence of mesenchymal stem cells in tumors and metastatic sites. These animals also exhibited decreased percentages of regulatory T lymphocytes and myeloid-derived suppressor cells in spleens but increased activated CD8+ cells and the IFNγ/IL-10 ratio. Therefore, thyroid hormones modulate the cellular and cytokine content of the breast tumor microenvironment. A better understanding of the mechanisms involved in these effects could be a starting point for the discovery of new therapeutic targets for breast cancer.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2021 |
|---|---|
| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:28 |
|---|---|
| Enthalten in: |
Endocrine-related cancer - 28(2021), 7 vom: 31. Mai, Seite 403-418 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Sterle, Helena Andrea [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
130068-27-8 |
|---|
| Anmerkungen: |
Date Completed 14.04.2022 Date Revised 14.04.2022 published: Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1530/ERC-20-0277 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM324617542 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM324617542 | ||
| 003 | DE-627 | ||
| 005 | 20231225190713.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2021 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1530/ERC-20-0277 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1082.xml |
| 035 | |a (DE-627)NLM324617542 | ||
| 035 | |a (NLM)33908371 | ||
| 035 | |a (PII)ERC-20-0277 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Sterle, Helena Andrea |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Thyroid status regulates the tumor microenvironment delineating breast cancer fate |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 14.04.2022 | ||
| 500 | |a Date Revised 14.04.2022 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a The patient's hormonal context plays a crucial role in the outcome of cancer. However, the association between thyroid disease and breast cancer risk remains unclear. We evaluated the effect of thyroid status on breast cancer growth and dissemination in an immunocompetent mouse model. For this, hyperthyroid and hypothyroid Balb/c mice were orthotopically inoculated with triple-negative breast cancer 4T1 cells. Tumors from hyperthyroid mice showed an increased growth rate and an immunosuppressive tumor microenvironment, characterized by increased IL-10 levels and decreased percentage of activated cytotoxic T cells. On the other hand, delayed tumor growth in hypothyroid animals was associated with increased tumor infiltration of activated CD8+ cells and a high IFNγ/IL-10 ratio. Paradoxically, hypothyroid mice developed a higher number of lung metastasis than hyperthyroid animals. This was related to an increased secretion of tumor CCL2 and an immunosuppressive systemic environment, with increased proportion of regulatory T cells and IL-10 levels in spleens. A lower number of lung metastasis in hyperthyroid mice was related to the reduced presence of mesenchymal stem cells in tumors and metastatic sites. These animals also exhibited decreased percentages of regulatory T lymphocytes and myeloid-derived suppressor cells in spleens but increased activated CD8+ cells and the IFNγ/IL-10 ratio. Therefore, thyroid hormones modulate the cellular and cytokine content of the breast tumor microenvironment. A better understanding of the mechanisms involved in these effects could be a starting point for the discovery of new therapeutic targets for breast cancer | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a antitumor immunity | |
| 650 | 4 | |a breast cancer | |
| 650 | 4 | |a hyperthyroidism | |
| 650 | 4 | |a hypothyroidism | |
| 650 | 4 | |a mesenchymal stem cells | |
| 650 | 7 | |a Interleukin-10 |2 NLM | |
| 650 | 7 | |a 130068-27-8 |2 NLM | |
| 700 | 1 | |a Hildebrandt, Ximena |e verfasserin |4 aut | |
| 700 | 1 | |a Valenzuela Álvarez, Matías |e verfasserin |4 aut | |
| 700 | 1 | |a Paulazo, María Alejandra |e verfasserin |4 aut | |
| 700 | 1 | |a Gutierrez, Luciana Mariel |e verfasserin |4 aut | |
| 700 | 1 | |a Klecha, Alicia Juana |e verfasserin |4 aut | |
| 700 | 1 | |a Cayrol, Florencia |e verfasserin |4 aut | |
| 700 | 1 | |a Díaz Flaqué, María Celeste |e verfasserin |4 aut | |
| 700 | 1 | |a Rosemblit, Cinthia |e verfasserin |4 aut | |
| 700 | 1 | |a Barreiro Arcos, María Laura |e verfasserin |4 aut | |
| 700 | 1 | |a Colombo, Lucas |e verfasserin |4 aut | |
| 700 | 1 | |a Bolontrade, Marcela Fabiana |e verfasserin |4 aut | |
| 700 | 1 | |a Medina, Vanina Araceli |e verfasserin |4 aut | |
| 700 | 1 | |a Cremaschi, Graciela Alicia |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Endocrine-related cancer |d 1997 |g 28(2021), 7 vom: 31. Mai, Seite 403-418 |w (DE-627)NLM093797834 |x 1479-6821 |7 nnns |
| 773 | 1 | 8 | |g volume:28 |g year:2021 |g number:7 |g day:31 |g month:05 |g pages:403-418 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1530/ERC-20-0277 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 28 |j 2021 |e 7 |b 31 |c 05 |h 403-418 | ||