Cargando…
Utilization of adipocyte-derived lipids and enhanced intracellular trafficking of fatty acids contribute to breast cancer progression
BACKGROUND: To determine whether adipocyte-derived lipids could be transferred into breast cancer cells and investigate the underlying mechanisms of subsequent lipolysis and fatty acid trafficking in breast cancer cells. METHODS: A Transwell co-culture system was used in which human breast cancer ce...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6006729/ https://www.ncbi.nlm.nih.gov/pubmed/29914512 http://dx.doi.org/10.1186/s12964-018-0221-6 |
_version_ | 1783332895953256448 |
---|---|
author | Yang, Dejuan Li, Yunhai Xing, Lei Tan, Yiqing Sun, Jiazheng Zeng, Beilei Xiang, Tingxiu Tan, Jinxiang Ren, Guosheng Wang, Yuanyuan |
author_facet | Yang, Dejuan Li, Yunhai Xing, Lei Tan, Yiqing Sun, Jiazheng Zeng, Beilei Xiang, Tingxiu Tan, Jinxiang Ren, Guosheng Wang, Yuanyuan |
author_sort | Yang, Dejuan |
collection | PubMed |
description | BACKGROUND: To determine whether adipocyte-derived lipids could be transferred into breast cancer cells and investigate the underlying mechanisms of subsequent lipolysis and fatty acid trafficking in breast cancer cells. METHODS: A Transwell co-culture system was used in which human breast cancer cells were cultured in the absence or presence of differentiated murine 3 T3-L1 adipocytes. Migration/invasion and proliferation abilities were compared between breast cancer cells that were cultivated alone and those co-cultivated with mature adipocytes. The ability of lipolysis in breast cancer cells were measured, as well as the expression of the rate-limiting lipase ATGL and fatty acid transporter FABP5. ATGL and FABP5 were then ablated to investigate their impact on the aggressiveness of breast cancer cells that were surrounded by adipocytes. Further, immunohistochemistry was performed to detect differential expression of ATGL and FABP5 in breast cancer tissue sections. RESULTS: The migration and invasion abilities of cancer cells were significantly enhanced after co-culture with adipocytes, accompanied by elevated lipolysis and expression of ATGL and FABP5. Abrogation of ATGL and FABP5 sharply attenuated the malignancy of co-cultivated breast cancer cells. However, this phenomenon was not observed if a lipid emulsion was added to the culture medium to substitute for adipocytes. Furthermore, epithelial-mesenchymal transaction was induced in co-cultivated breast cancer cells. That may partially due to the stimulation of PPARβ/δ and MAPK, which was resulted from upregulation of FABP5. As evidenced by immunohistochemistry, ATGL and FABP5 also had higher expression levels at the invasive front of the breast tumor, in where the adipocytes abound, compared to the central area in tissue specimens. CONCLUSIONS: Lipid originating from tumor-surrounding adipocytes could be transferred into breast cancer cells. Adipocyte-cancer cell crosstalk rather than lipids alone induced upregulation of lipases and fatty acid transport protein in cancer cells to utilize stored lipids for tumor progression. The increased expression of the key lipase ATGL and intracellular fatty acid trafficking protein FABP5 played crucial roles in this process via fueling or signaling. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12964-018-0221-6) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6006729 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-60067292018-06-26 Utilization of adipocyte-derived lipids and enhanced intracellular trafficking of fatty acids contribute to breast cancer progression Yang, Dejuan Li, Yunhai Xing, Lei Tan, Yiqing Sun, Jiazheng Zeng, Beilei Xiang, Tingxiu Tan, Jinxiang Ren, Guosheng Wang, Yuanyuan Cell Commun Signal Research BACKGROUND: To determine whether adipocyte-derived lipids could be transferred into breast cancer cells and investigate the underlying mechanisms of subsequent lipolysis and fatty acid trafficking in breast cancer cells. METHODS: A Transwell co-culture system was used in which human breast cancer cells were cultured in the absence or presence of differentiated murine 3 T3-L1 adipocytes. Migration/invasion and proliferation abilities were compared between breast cancer cells that were cultivated alone and those co-cultivated with mature adipocytes. The ability of lipolysis in breast cancer cells were measured, as well as the expression of the rate-limiting lipase ATGL and fatty acid transporter FABP5. ATGL and FABP5 were then ablated to investigate their impact on the aggressiveness of breast cancer cells that were surrounded by adipocytes. Further, immunohistochemistry was performed to detect differential expression of ATGL and FABP5 in breast cancer tissue sections. RESULTS: The migration and invasion abilities of cancer cells were significantly enhanced after co-culture with adipocytes, accompanied by elevated lipolysis and expression of ATGL and FABP5. Abrogation of ATGL and FABP5 sharply attenuated the malignancy of co-cultivated breast cancer cells. However, this phenomenon was not observed if a lipid emulsion was added to the culture medium to substitute for adipocytes. Furthermore, epithelial-mesenchymal transaction was induced in co-cultivated breast cancer cells. That may partially due to the stimulation of PPARβ/δ and MAPK, which was resulted from upregulation of FABP5. As evidenced by immunohistochemistry, ATGL and FABP5 also had higher expression levels at the invasive front of the breast tumor, in where the adipocytes abound, compared to the central area in tissue specimens. CONCLUSIONS: Lipid originating from tumor-surrounding adipocytes could be transferred into breast cancer cells. Adipocyte-cancer cell crosstalk rather than lipids alone induced upregulation of lipases and fatty acid transport protein in cancer cells to utilize stored lipids for tumor progression. The increased expression of the key lipase ATGL and intracellular fatty acid trafficking protein FABP5 played crucial roles in this process via fueling or signaling. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12964-018-0221-6) contains supplementary material, which is available to authorized users. BioMed Central 2018-06-18 /pmc/articles/PMC6006729/ /pubmed/29914512 http://dx.doi.org/10.1186/s12964-018-0221-6 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 Yang, Dejuan Li, Yunhai Xing, Lei Tan, Yiqing Sun, Jiazheng Zeng, Beilei Xiang, Tingxiu Tan, Jinxiang Ren, Guosheng Wang, Yuanyuan Utilization of adipocyte-derived lipids and enhanced intracellular trafficking of fatty acids contribute to breast cancer progression |
title | Utilization of adipocyte-derived lipids and enhanced intracellular trafficking of fatty acids contribute to breast cancer progression |
title_full | Utilization of adipocyte-derived lipids and enhanced intracellular trafficking of fatty acids contribute to breast cancer progression |
title_fullStr | Utilization of adipocyte-derived lipids and enhanced intracellular trafficking of fatty acids contribute to breast cancer progression |
title_full_unstemmed | Utilization of adipocyte-derived lipids and enhanced intracellular trafficking of fatty acids contribute to breast cancer progression |
title_short | Utilization of adipocyte-derived lipids and enhanced intracellular trafficking of fatty acids contribute to breast cancer progression |
title_sort | utilization of adipocyte-derived lipids and enhanced intracellular trafficking of fatty acids contribute to breast cancer progression |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6006729/ https://www.ncbi.nlm.nih.gov/pubmed/29914512 http://dx.doi.org/10.1186/s12964-018-0221-6 |
work_keys_str_mv | AT yangdejuan utilizationofadipocytederivedlipidsandenhancedintracellulartraffickingoffattyacidscontributetobreastcancerprogression AT liyunhai utilizationofadipocytederivedlipidsandenhancedintracellulartraffickingoffattyacidscontributetobreastcancerprogression AT xinglei utilizationofadipocytederivedlipidsandenhancedintracellulartraffickingoffattyacidscontributetobreastcancerprogression AT tanyiqing utilizationofadipocytederivedlipidsandenhancedintracellulartraffickingoffattyacidscontributetobreastcancerprogression AT sunjiazheng utilizationofadipocytederivedlipidsandenhancedintracellulartraffickingoffattyacidscontributetobreastcancerprogression AT zengbeilei utilizationofadipocytederivedlipidsandenhancedintracellulartraffickingoffattyacidscontributetobreastcancerprogression AT xiangtingxiu utilizationofadipocytederivedlipidsandenhancedintracellulartraffickingoffattyacidscontributetobreastcancerprogression AT tanjinxiang utilizationofadipocytederivedlipidsandenhancedintracellulartraffickingoffattyacidscontributetobreastcancerprogression AT renguosheng utilizationofadipocytederivedlipidsandenhancedintracellulartraffickingoffattyacidscontributetobreastcancerprogression AT wangyuanyuan utilizationofadipocytederivedlipidsandenhancedintracellulartraffickingoffattyacidscontributetobreastcancerprogression |