دورية أكاديمية
Generation and Characterization of a Tumor Stromal Microenvironment and Analysis of Its Interplay with Breast Cancer Cells: An In Vitro Model to Study Breast Cancer-Associated Fibroblast Inactivation
| العنوان: | Generation and Characterization of a Tumor Stromal Microenvironment and Analysis of Its Interplay with Breast Cancer Cells: An In Vitro Model to Study Breast Cancer-Associated Fibroblast Inactivation |
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| المؤلفون: | Veronica Romano, Maria Rosaria Ruocco, Pietro Carotenuto, Anna Barbato, Alessandro Venuta, Vittoria Acampora, Sabrina De Lella, Elena Vigliar, Antonino Iaccarino, Giancarlo Troncone, Gaetano Calì, Luigi Insabato, Daniela Russo, Brunella Franco, Stefania Masone, Nunzio Velotti, Antonello Accurso, Tommaso Pellegrino, Giuseppe Fiume, Immacolata Belviso, Stefania Montagnani, Angelica Avagliano, Alessandro Arcucci |
| المصدر: | International Journal of Molecular Sciences, Vol 23, Iss 12, p 6875 (2022) |
| بيانات النشر: | MDPI AG, 2022. |
| سنة النشر: | 2022 |
| المجموعة: | LCC:Biology (General) LCC:Chemistry |
| مصطلحات موضوعية: | breast cancer, breast cancer-associated fibroblasts, aggregates, breast cancer cells, deactivation, conditioned medium, Biology (General), QH301-705.5, Chemistry, QD1-999 |
| الوصف: | Breast cancer-associated fibroblasts (BCAFs), the most abundant non-cancer stromal cells of the breast tumor microenvironment (TME), dramatically sustain breast cancer (BC) progression by interacting with BC cells. BCAFs, as well as myofibroblasts, display an up regulation of activation and inflammation markers represented by α-smooth muscle actin (α-SMA) and cyclooxygenase 2 (COX-2). BCAF aggregates have been identified in the peripheral blood of metastatic BC patients. We generated an in vitro stromal model consisting of human primary BCAFs grown as monolayers or 3D cell aggregates, namely spheroids and reverted BCAFs, obtained from BCAF spheroids reverted to 2D cell adhesion growth after 216 h of 3D culture. We firstly evaluated the state of activation and inflammation and the mesenchymal status of the BCAF monolayers, BCAF spheroids and reverted BCAFs. Then, we analyzed the MCF-7 cell viability and migration following treatment with conditioned media from the different BCAF cultures. After 216 h of 3D culture, the BCAFs acquired an inactivated phenotype, associated with a significant reduction in α-SMA and COX-2 protein expression. The deactivation of the BCAF spheroids at 216 h was further confirmed by the cytostatic effect exerted by their conditioned medium on MCF-7 cells. Interestingly, the reverted BCAFs also retained a less activated phenotype as indicated by α-SMA protein expression reduction. Furthermore, the reverted BCAFs exhibited a reduced pro-tumor phenotype as indicated by the anti-migratory effect exerted by their conditioned medium on MCF-7 cells. The deactivation of BCAFs without drug treatment is possible and leads to a reduced capability of BCAFs to sustain BC progression in vitro. Consequently, this study could be a starting point to develop new therapeutic strategies targeting BCAFs and their interactions with cancer cells. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1422-0067 1661-6596 |
| العلاقة: | https://www.mdpi.com/1422-0067/23/12/6875Test; https://doaj.org/toc/1661-6596Test; https://doaj.org/toc/1422-0067Test |
| DOI: | 10.3390/ijms23126875 |
| الوصول الحر: | https://doaj.org/article/dd6cb0f278da438b9f0447138a88f2b4Test |
| رقم الانضمام: | edsdoj.6cb0f278da438b9f0447138a88f2b4 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 14220067 16616596 |
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| DOI: | 10.3390/ijms23126875 |