Adipose Tissue from Lean and Obese Mice Induces a Mesenchymal to Epithelial Transition-Like Effect in Triple Negative Breast Cancers Cells Grown in 3-Dimensional Culture
Breast cancer is the second leading cause of cancer-related mortality among women globally with obesity being one risk factor. Obese breast cancer patients have at least a 30% increased risk of death from breast cancer compared to non-obese breast cancer patients because they present with larger tum...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/17/6439 |
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| author | Emmanuel C. Asante Nikitha K. Pallegar Alica J. Hoffmann Alicia M. Viloria-Petit Sherri L. Christian |
| author_facet | Emmanuel C. Asante Nikitha K. Pallegar Alica J. Hoffmann Alicia M. Viloria-Petit Sherri L. Christian |
| author_sort | Emmanuel C. Asante |
| collection | DOAJ |
| description | Breast cancer is the second leading cause of cancer-related mortality among women globally with obesity being one risk factor. Obese breast cancer patients have at least a 30% increased risk of death from breast cancer compared to non-obese breast cancer patients because they present with larger tumors and generally have increased rates of metastasis. Moreover, obese breast cancer patients respond more poorly to treatment compared to non-obese patients, particularly pre-menopausal women diagnosed with triple negative breast cancer (TNBC). To help understand the molecular mechanisms underlying the increased metastasis associated with obesity, we previously established a three-dimensional culture system that permits the co-culture of adipocytes and TNBC cells in a manner that mimics an in vivo milieu. Using this system, we demonstrate that white adipose tissue from both lean and obese mice can induce a partial mesenchymal-to-epithelial transition (MET). Triple negative breast cancer cells adopt an epithelial morphology and have an increased expression of some epithelial markers, but they maintain the expression of mesenchymal markers, furnishing the breast cancer cells with hybrid properties that are associated with more aggressive tumors. Thus, these data suggest that adipose tissue has the potential to promote secondary tumor formation in lean and obese women. Further work is needed to determine if targeting the partial MET induced by adipose tissue could reduce metastasis. |
| first_indexed | 2024-03-10T16:34:55Z |
| format | Article |
| id | doaj.art-77c2406501514a2489675046085a0e55 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T16:34:55Z |
| publishDate | 2020-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-77c2406501514a2489675046085a0e552023-11-20T12:31:41ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-09-012117643910.3390/ijms21176439Adipose Tissue from Lean and Obese Mice Induces a Mesenchymal to Epithelial Transition-Like Effect in Triple Negative Breast Cancers Cells Grown in 3-Dimensional CultureEmmanuel C. Asante0Nikitha K. Pallegar1Alica J. Hoffmann2Alicia M. Viloria-Petit3Sherri L. Christian4Department of Biochemistry, Memorial University of Newfoundland, St. John’s, NL A1B 3X9, CanadaDepartment of Biochemistry, Memorial University of Newfoundland, St. John’s, NL A1B 3X9, CanadaDepartment of Biochemistry, Memorial University of Newfoundland, St. John’s, NL A1B 3X9, CanadaDepartment of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, CanadaDepartment of Biochemistry, Memorial University of Newfoundland, St. John’s, NL A1B 3X9, CanadaBreast cancer is the second leading cause of cancer-related mortality among women globally with obesity being one risk factor. Obese breast cancer patients have at least a 30% increased risk of death from breast cancer compared to non-obese breast cancer patients because they present with larger tumors and generally have increased rates of metastasis. Moreover, obese breast cancer patients respond more poorly to treatment compared to non-obese patients, particularly pre-menopausal women diagnosed with triple negative breast cancer (TNBC). To help understand the molecular mechanisms underlying the increased metastasis associated with obesity, we previously established a three-dimensional culture system that permits the co-culture of adipocytes and TNBC cells in a manner that mimics an in vivo milieu. Using this system, we demonstrate that white adipose tissue from both lean and obese mice can induce a partial mesenchymal-to-epithelial transition (MET). Triple negative breast cancer cells adopt an epithelial morphology and have an increased expression of some epithelial markers, but they maintain the expression of mesenchymal markers, furnishing the breast cancer cells with hybrid properties that are associated with more aggressive tumors. Thus, these data suggest that adipose tissue has the potential to promote secondary tumor formation in lean and obese women. Further work is needed to determine if targeting the partial MET induced by adipose tissue could reduce metastasis.https://www.mdpi.com/1422-0067/21/17/6439METmetastasisbreast cancertriple negative breast cancerobesityadipose tissue |
| spellingShingle | Emmanuel C. Asante Nikitha K. Pallegar Alica J. Hoffmann Alicia M. Viloria-Petit Sherri L. Christian Adipose Tissue from Lean and Obese Mice Induces a Mesenchymal to Epithelial Transition-Like Effect in Triple Negative Breast Cancers Cells Grown in 3-Dimensional Culture International Journal of Molecular Sciences MET metastasis breast cancer triple negative breast cancer obesity adipose tissue |
| title | Adipose Tissue from Lean and Obese Mice Induces a Mesenchymal to Epithelial Transition-Like Effect in Triple Negative Breast Cancers Cells Grown in 3-Dimensional Culture |
| title_full | Adipose Tissue from Lean and Obese Mice Induces a Mesenchymal to Epithelial Transition-Like Effect in Triple Negative Breast Cancers Cells Grown in 3-Dimensional Culture |
| title_fullStr | Adipose Tissue from Lean and Obese Mice Induces a Mesenchymal to Epithelial Transition-Like Effect in Triple Negative Breast Cancers Cells Grown in 3-Dimensional Culture |
| title_full_unstemmed | Adipose Tissue from Lean and Obese Mice Induces a Mesenchymal to Epithelial Transition-Like Effect in Triple Negative Breast Cancers Cells Grown in 3-Dimensional Culture |
| title_short | Adipose Tissue from Lean and Obese Mice Induces a Mesenchymal to Epithelial Transition-Like Effect in Triple Negative Breast Cancers Cells Grown in 3-Dimensional Culture |
| title_sort | adipose tissue from lean and obese mice induces a mesenchymal to epithelial transition like effect in triple negative breast cancers cells grown in 3 dimensional culture |
| topic | MET metastasis breast cancer triple negative breast cancer obesity adipose tissue |
| url | https://www.mdpi.com/1422-0067/21/17/6439 |
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