Macrophages Upregulate Estrogen Receptor Expression in the Model of Obesity-Associated Breast Carcinoma
Breast cancer (BC) and obesity are two heterogeneous conditions with a tremendous impact on health. BC is the most commonly diagnosed neoplasm and the leading cause of cancer-related mortality among women, and the prevalence of obesity in women worldwide reaches pandemic proportions. Obesity is a si...
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| Format: | Article |
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MDPI AG
2022-09-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/18/2844 |
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| author | Daniela Nahmias Blank Esther Hermano Amir Sonnenblick Ofra Maimon Ariel M. Rubinstein Emmy Drai Bella Maly Israel Vlodavsky Aron Popovtzer Tamar Peretz Amichay Meirovitz Michael Elkin |
| author_facet | Daniela Nahmias Blank Esther Hermano Amir Sonnenblick Ofra Maimon Ariel M. Rubinstein Emmy Drai Bella Maly Israel Vlodavsky Aron Popovtzer Tamar Peretz Amichay Meirovitz Michael Elkin |
| author_sort | Daniela Nahmias Blank |
| collection | DOAJ |
| description | Breast cancer (BC) and obesity are two heterogeneous conditions with a tremendous impact on health. BC is the most commonly diagnosed neoplasm and the leading cause of cancer-related mortality among women, and the prevalence of obesity in women worldwide reaches pandemic proportions. Obesity is a significant risk factor for both incidence and worse prognosis in estrogen receptor positive (ER+) BC. Yet, the mechanisms underlying the association between excess adiposity and increased risk/therapy resistance/poorer outcome of ER+, but not ER−negative (ER−), BC are not fully understood. Tumor-promoting action of obesity, predominantly in ER + BC patients, is often attributed to the augmented production of estrogen in ‘obese’ adipose tissue. However, in addition to the estrogen production, expression levels of ER represent a key determinant in hormone-driven breast tumorigenesis and therapy response. Here, utilizing in vitro and in vivo models of BC, we show that macrophages, whose adverse activation by obesogenic substances is fueled by heparanase (extracellular matrix-degrading enzyme), are capable of upregulating ER expression in tumor cells, in the setting of obesity-associated BC. These findings underscore a previously unknown mechanism through which interplay between cellular/extracellular elements of obesity-associated BC microenvironment influences estrogen sensitivity—a critical component in hormone-related cancer progression and resistance to therapy. |
| first_indexed | 2024-03-10T00:26:31Z |
| format | Article |
| id | doaj.art-43e814592e8b4fbd90b25060eb5d6b0d |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T00:26:31Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-43e814592e8b4fbd90b25060eb5d6b0d2023-11-23T15:33:11ZengMDPI AGCells2073-44092022-09-011118284410.3390/cells11182844Macrophages Upregulate Estrogen Receptor Expression in the Model of Obesity-Associated Breast CarcinomaDaniela Nahmias Blank0Esther Hermano1Amir Sonnenblick2Ofra Maimon3Ariel M. Rubinstein4Emmy Drai5Bella Maly6Israel Vlodavsky7Aron Popovtzer8Tamar Peretz9Amichay Meirovitz10Michael Elkin11Sharett Institute of Oncology, Hadassah-Hebrew University Medical Center, Jerusalem 91120, IsraelSharett Institute of Oncology, Hadassah-Hebrew University Medical Center, Jerusalem 91120, IsraelOncology Division, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 64239, IsraelSharett Institute of Oncology, Hadassah-Hebrew University Medical Center, Jerusalem 91120, IsraelSharett Institute of Oncology, Hadassah-Hebrew University Medical Center, Jerusalem 91120, IsraelSharett Institute of Oncology, Hadassah-Hebrew University Medical Center, Jerusalem 91120, IsraelDepartment of Pathology, Hadassah-Hebrew University Medical Center, Jerusalem 91120, IsraelCancer and Vascular Biology Research Center, The Rappaport Faculty of Medicine, Technion, Haifa 31096, IsraelSharett Institute of Oncology, Hadassah-Hebrew University Medical Center, Jerusalem 91120, IsraelSharett Institute of Oncology, Hadassah-Hebrew University Medical Center, Jerusalem 91120, IsraelSharett Institute of Oncology, Hadassah-Hebrew University Medical Center, Jerusalem 91120, IsraelSharett Institute of Oncology, Hadassah-Hebrew University Medical Center, Jerusalem 91120, IsraelBreast cancer (BC) and obesity are two heterogeneous conditions with a tremendous impact on health. BC is the most commonly diagnosed neoplasm and the leading cause of cancer-related mortality among women, and the prevalence of obesity in women worldwide reaches pandemic proportions. Obesity is a significant risk factor for both incidence and worse prognosis in estrogen receptor positive (ER+) BC. Yet, the mechanisms underlying the association between excess adiposity and increased risk/therapy resistance/poorer outcome of ER+, but not ER−negative (ER−), BC are not fully understood. Tumor-promoting action of obesity, predominantly in ER + BC patients, is often attributed to the augmented production of estrogen in ‘obese’ adipose tissue. However, in addition to the estrogen production, expression levels of ER represent a key determinant in hormone-driven breast tumorigenesis and therapy response. Here, utilizing in vitro and in vivo models of BC, we show that macrophages, whose adverse activation by obesogenic substances is fueled by heparanase (extracellular matrix-degrading enzyme), are capable of upregulating ER expression in tumor cells, in the setting of obesity-associated BC. These findings underscore a previously unknown mechanism through which interplay between cellular/extracellular elements of obesity-associated BC microenvironment influences estrogen sensitivity—a critical component in hormone-related cancer progression and resistance to therapy.https://www.mdpi.com/2073-4409/11/18/2844breast cancerheparanaseobesityestrogenestrogen receptor αmacrophages |
| spellingShingle | Daniela Nahmias Blank Esther Hermano Amir Sonnenblick Ofra Maimon Ariel M. Rubinstein Emmy Drai Bella Maly Israel Vlodavsky Aron Popovtzer Tamar Peretz Amichay Meirovitz Michael Elkin Macrophages Upregulate Estrogen Receptor Expression in the Model of Obesity-Associated Breast Carcinoma Cells breast cancer heparanase obesity estrogen estrogen receptor α macrophages |
| title | Macrophages Upregulate Estrogen Receptor Expression in the Model of Obesity-Associated Breast Carcinoma |
| title_full | Macrophages Upregulate Estrogen Receptor Expression in the Model of Obesity-Associated Breast Carcinoma |
| title_fullStr | Macrophages Upregulate Estrogen Receptor Expression in the Model of Obesity-Associated Breast Carcinoma |
| title_full_unstemmed | Macrophages Upregulate Estrogen Receptor Expression in the Model of Obesity-Associated Breast Carcinoma |
| title_short | Macrophages Upregulate Estrogen Receptor Expression in the Model of Obesity-Associated Breast Carcinoma |
| title_sort | macrophages upregulate estrogen receptor expression in the model of obesity associated breast carcinoma |
| topic | breast cancer heparanase obesity estrogen estrogen receptor α macrophages |
| url | https://www.mdpi.com/2073-4409/11/18/2844 |
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