Permanent Pro-Tumorigenic Shift in Adipose Tissue-Derived Mesenchymal Stromal Cells Induced by Breast Malignancy
During cancer progression, breast tumor cells interact with adjacent adipose tissue, which has been shown to be engaged in cancer aggressiveness. However, the tumor-directed changes in adipose tissue-resident stromal cells affected by the tumor−stroma communication are still poorly underst...
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MDPI AG
2020-02-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/9/2/480 |
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| author | Jana Plava Marina Cihova Monika Burikova Martin Bohac Marian Adamkov Slavka Drahosova Dominika Rusnakova Daniel Pindak Marian Karaba Jan Simo Michal Mego Lubos Danisovic Lucia Kucerova Svetlana Miklikova |
| author_facet | Jana Plava Marina Cihova Monika Burikova Martin Bohac Marian Adamkov Slavka Drahosova Dominika Rusnakova Daniel Pindak Marian Karaba Jan Simo Michal Mego Lubos Danisovic Lucia Kucerova Svetlana Miklikova |
| author_sort | Jana Plava |
| collection | DOAJ |
| description | During cancer progression, breast tumor cells interact with adjacent adipose tissue, which has been shown to be engaged in cancer aggressiveness. However, the tumor-directed changes in adipose tissue-resident stromal cells affected by the tumor−stroma communication are still poorly understood. The acquired changes might remain in the tissue even after tumor removal and may contribute to tumor relapse. We investigated functional properties (migratory capacity, expression and secretion profile) of mesenchymal stromal cells isolated from healthy (<i>n</i> = 9) and tumor-distant breast adipose tissue (<i>n</i> = 32). Cancer patient-derived mesenchymal stromal cells (MSCs) (MSC-CA) exhibited a significantly disarranged secretion profile and proliferation potential. Co-culture with MDA-MB-231, T47D and JIMT-1, representing different subtypes of breast cancer, was used to analyze the effect of MSCs on proliferation, invasion and tumorigenicity. The MSC-CA enhanced tumorigenicity and altered xenograft composition in immunodeficient mice. Histological analysis revealed collective cell invasion with a specific invasive front of EMT-positive tumor cells as well as invasion of cancer cells to the nerve-surrounding space. This study identifies that adipose tissue-derived mesenchymal stromal cells are primed and permanently altered by tumor presence in breast tissue and have the potential to increase tumor cell invasive ability through the activation of epithelial-to-mesenchymal transition in tumor cells. |
| first_indexed | 2024-03-12T05:55:12Z |
| format | Article |
| id | doaj.art-27d0e0c63f5c40a79e446318c4a463d3 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T05:55:12Z |
| publishDate | 2020-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-27d0e0c63f5c40a79e446318c4a463d32023-09-03T04:34:22ZengMDPI AGCells2073-44092020-02-019248010.3390/cells9020480cells9020480Permanent Pro-Tumorigenic Shift in Adipose Tissue-Derived Mesenchymal Stromal Cells Induced by Breast MalignancyJana Plava0Marina Cihova1Monika Burikova2Martin Bohac3Marian Adamkov4Slavka Drahosova5Dominika Rusnakova6Daniel Pindak7Marian Karaba8Jan Simo9Michal Mego10Lubos Danisovic11Lucia Kucerova12Svetlana Miklikova13Cancer Research Institute, Biomedical Research Center, University Science Park for Biomedicine, Slovak Academy of Sciences, 845 05 Bratislava, SlovakiaCancer Research Institute, Biomedical Research Center, University Science Park for Biomedicine, Slovak Academy of Sciences, 845 05 Bratislava, SlovakiaCancer Research Institute, Biomedical Research Center, University Science Park for Biomedicine, Slovak Academy of Sciences, 845 05 Bratislava, Slovakia2nd Department of Oncology, Faculty of Medicine, Comenius University, National Cancer Institute, Klenova 1, 833 10 Bratislava, SlovakiaComenius University Bratislava, Jessenius Faculty of Medicine Martin, Department of Histology and Embryology, 036 01 Martin, SlovakiaHermes LabSystems, s.r.o., 831 06 Bratislava, SlovakiaInstitute of Medical Biology, Genetics and Clinical Genetics, Faculty of Medicine, Comenius University, 813 72 Bratislava, SlovakiaInstitute of Medical Biology, Genetics and Clinical Genetics, Faculty of Medicine, Comenius University, 813 72 Bratislava, SlovakiaInstitute of Medical Biology, Genetics and Clinical Genetics, Faculty of Medicine, Comenius University, 813 72 Bratislava, SlovakiaInstitute of Medical Biology, Genetics and Clinical Genetics, Faculty of Medicine, Comenius University, 813 72 Bratislava, Slovakia2nd Department of Oncology, Faculty of Medicine, Comenius University, National Cancer Institute, Klenova 1, 833 10 Bratislava, SlovakiaDepartment of Oncosurgery, National Cancer Institute, Klenova 1, 833 10 Bratislava, SlovakiaCancer Research Institute, Biomedical Research Center, University Science Park for Biomedicine, Slovak Academy of Sciences, 845 05 Bratislava, SlovakiaCancer Research Institute, Biomedical Research Center, University Science Park for Biomedicine, Slovak Academy of Sciences, 845 05 Bratislava, SlovakiaDuring cancer progression, breast tumor cells interact with adjacent adipose tissue, which has been shown to be engaged in cancer aggressiveness. However, the tumor-directed changes in adipose tissue-resident stromal cells affected by the tumor−stroma communication are still poorly understood. The acquired changes might remain in the tissue even after tumor removal and may contribute to tumor relapse. We investigated functional properties (migratory capacity, expression and secretion profile) of mesenchymal stromal cells isolated from healthy (<i>n</i> = 9) and tumor-distant breast adipose tissue (<i>n</i> = 32). Cancer patient-derived mesenchymal stromal cells (MSCs) (MSC-CA) exhibited a significantly disarranged secretion profile and proliferation potential. Co-culture with MDA-MB-231, T47D and JIMT-1, representing different subtypes of breast cancer, was used to analyze the effect of MSCs on proliferation, invasion and tumorigenicity. The MSC-CA enhanced tumorigenicity and altered xenograft composition in immunodeficient mice. Histological analysis revealed collective cell invasion with a specific invasive front of EMT-positive tumor cells as well as invasion of cancer cells to the nerve-surrounding space. This study identifies that adipose tissue-derived mesenchymal stromal cells are primed and permanently altered by tumor presence in breast tissue and have the potential to increase tumor cell invasive ability through the activation of epithelial-to-mesenchymal transition in tumor cells.https://www.mdpi.com/2073-4409/9/2/480mesenchymal stromal cellsadipose tissuebreast cancertumor microenvironmentperineural invasion |
| spellingShingle | Jana Plava Marina Cihova Monika Burikova Martin Bohac Marian Adamkov Slavka Drahosova Dominika Rusnakova Daniel Pindak Marian Karaba Jan Simo Michal Mego Lubos Danisovic Lucia Kucerova Svetlana Miklikova Permanent Pro-Tumorigenic Shift in Adipose Tissue-Derived Mesenchymal Stromal Cells Induced by Breast Malignancy Cells mesenchymal stromal cells adipose tissue breast cancer tumor microenvironment perineural invasion |
| title | Permanent Pro-Tumorigenic Shift in Adipose Tissue-Derived Mesenchymal Stromal Cells Induced by Breast Malignancy |
| title_full | Permanent Pro-Tumorigenic Shift in Adipose Tissue-Derived Mesenchymal Stromal Cells Induced by Breast Malignancy |
| title_fullStr | Permanent Pro-Tumorigenic Shift in Adipose Tissue-Derived Mesenchymal Stromal Cells Induced by Breast Malignancy |
| title_full_unstemmed | Permanent Pro-Tumorigenic Shift in Adipose Tissue-Derived Mesenchymal Stromal Cells Induced by Breast Malignancy |
| title_short | Permanent Pro-Tumorigenic Shift in Adipose Tissue-Derived Mesenchymal Stromal Cells Induced by Breast Malignancy |
| title_sort | permanent pro tumorigenic shift in adipose tissue derived mesenchymal stromal cells induced by breast malignancy |
| topic | mesenchymal stromal cells adipose tissue breast cancer tumor microenvironment perineural invasion |
| url | https://www.mdpi.com/2073-4409/9/2/480 |
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