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Protective role of all-trans retinoic acid (ATRA) against hypoxia-induced malignant potential of non-invasive breast tumor derived cells
BACKGROUND: The presence of hypoxic areas is common in all breast lesions but no data clearly correlate low oxygenation with the acquisition of malignant features by non-invasive cells, particularly by cells from ductal carcinoma in situ (DCIS), the most frequently diagnosed tumor in women. METHODS:...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6267073/ https://www.ncbi.nlm.nih.gov/pubmed/30497437 http://dx.doi.org/10.1186/s12885-018-5038-6 |
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author | Al-Qassab, Yasamin Grassilli, Silvia Brugnoli, Federica Vezzali, Federica Capitani, Silvano Bertagnolo, Valeria |
author_facet | Al-Qassab, Yasamin Grassilli, Silvia Brugnoli, Federica Vezzali, Federica Capitani, Silvano Bertagnolo, Valeria |
author_sort | Al-Qassab, Yasamin |
collection | PubMed |
description | BACKGROUND: The presence of hypoxic areas is common in all breast lesions but no data clearly correlate low oxygenation with the acquisition of malignant features by non-invasive cells, particularly by cells from ductal carcinoma in situ (DCIS), the most frequently diagnosed tumor in women. METHODS: By using a DCIS-derived cell line, we evaluated the effects of low oxygen availability on malignant features of non-invasive breast tumor cells and the possible role of all-trans retinoic acid (ATRA), a well-known anti-leukemic drug, in counteracting the effects of hypoxia. The involvement of the β2 isoform of PI-PLC (PLC-β2), an ATRA target in myeloid leukemia cells, was also investigated by specific modulation of the protein expression. RESULTS: We demonstrated that moderate hypoxia is sufficient to induce, in DCIS-derived cells, motility, epithelial-to-mesenchymal transition (EMT) and expression of the stem cell marker CD133, indicative of their increased malignant potential. Administration of ATRA supports the epithelial-like phenotype of DCIS-derived cells cultured under hypoxia and keeps down the number of CD133 positive cells, abrogating almost completely the effects of poor oxygenation. We also found that the mechanisms triggered by ATRA in non-invasive breast tumor cells cultured under hypoxia is in part mediated by PLC-β2, responsible to counteract the effects of low oxygen availability on CD133 levels. CONCLUSIONS: Overall, we assigned to hypoxia a role in increasing the malignant potential of DCIS-derived cells and we identified in ATRA, currently used in treatment of acute promyelocytic leukemia (APL), an agonist potentially useful in preventing malignant progression of non-invasive breast lesions showing hypoxic areas. |
format | Online Article Text |
id | pubmed-6267073 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-62670732018-12-05 Protective role of all-trans retinoic acid (ATRA) against hypoxia-induced malignant potential of non-invasive breast tumor derived cells Al-Qassab, Yasamin Grassilli, Silvia Brugnoli, Federica Vezzali, Federica Capitani, Silvano Bertagnolo, Valeria BMC Cancer Research Article BACKGROUND: The presence of hypoxic areas is common in all breast lesions but no data clearly correlate low oxygenation with the acquisition of malignant features by non-invasive cells, particularly by cells from ductal carcinoma in situ (DCIS), the most frequently diagnosed tumor in women. METHODS: By using a DCIS-derived cell line, we evaluated the effects of low oxygen availability on malignant features of non-invasive breast tumor cells and the possible role of all-trans retinoic acid (ATRA), a well-known anti-leukemic drug, in counteracting the effects of hypoxia. The involvement of the β2 isoform of PI-PLC (PLC-β2), an ATRA target in myeloid leukemia cells, was also investigated by specific modulation of the protein expression. RESULTS: We demonstrated that moderate hypoxia is sufficient to induce, in DCIS-derived cells, motility, epithelial-to-mesenchymal transition (EMT) and expression of the stem cell marker CD133, indicative of their increased malignant potential. Administration of ATRA supports the epithelial-like phenotype of DCIS-derived cells cultured under hypoxia and keeps down the number of CD133 positive cells, abrogating almost completely the effects of poor oxygenation. We also found that the mechanisms triggered by ATRA in non-invasive breast tumor cells cultured under hypoxia is in part mediated by PLC-β2, responsible to counteract the effects of low oxygen availability on CD133 levels. CONCLUSIONS: Overall, we assigned to hypoxia a role in increasing the malignant potential of DCIS-derived cells and we identified in ATRA, currently used in treatment of acute promyelocytic leukemia (APL), an agonist potentially useful in preventing malignant progression of non-invasive breast lesions showing hypoxic areas. BioMed Central 2018-11-29 /pmc/articles/PMC6267073/ /pubmed/30497437 http://dx.doi.org/10.1186/s12885-018-5038-6 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Al-Qassab, Yasamin Grassilli, Silvia Brugnoli, Federica Vezzali, Federica Capitani, Silvano Bertagnolo, Valeria Protective role of all-trans retinoic acid (ATRA) against hypoxia-induced malignant potential of non-invasive breast tumor derived cells |
title | Protective role of all-trans retinoic acid (ATRA) against hypoxia-induced malignant potential of non-invasive breast tumor derived cells |
title_full | Protective role of all-trans retinoic acid (ATRA) against hypoxia-induced malignant potential of non-invasive breast tumor derived cells |
title_fullStr | Protective role of all-trans retinoic acid (ATRA) against hypoxia-induced malignant potential of non-invasive breast tumor derived cells |
title_full_unstemmed | Protective role of all-trans retinoic acid (ATRA) against hypoxia-induced malignant potential of non-invasive breast tumor derived cells |
title_short | Protective role of all-trans retinoic acid (ATRA) against hypoxia-induced malignant potential of non-invasive breast tumor derived cells |
title_sort | protective role of all-trans retinoic acid (atra) against hypoxia-induced malignant potential of non-invasive breast tumor derived cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6267073/ https://www.ncbi.nlm.nih.gov/pubmed/30497437 http://dx.doi.org/10.1186/s12885-018-5038-6 |
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