Distinctive Properties of Endothelial Cells from Tumor and Normal Tissue in Human Breast Cancer
Tumor microenvironments shape aggressiveness and are largely maintained by the conditions of angiogenesis formation. Thus, endothelial cells’ (ECs) biological reactions are crucial to understand and control the design of efficient therapies. In this work, we used models of ECs to represent a breast...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-08-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/22/16/8862 |
| _version_ | 1797523575226236928 |
|---|---|
| author | Kinga Wilkus Klaudia Brodaczewska Arkadiusz Kajdasz Claudine Kieda |
| author_facet | Kinga Wilkus Klaudia Brodaczewska Arkadiusz Kajdasz Claudine Kieda |
| author_sort | Kinga Wilkus |
| collection | DOAJ |
| description | Tumor microenvironments shape aggressiveness and are largely maintained by the conditions of angiogenesis formation. Thus, endothelial cells’ (ECs) biological reactions are crucial to understand and control the design of efficient therapies. In this work, we used models of ECs to represent a breast cancer tumor site as well as the same, healthy tissue. Cells characterization was performed at the transcriptome and protein expression levels, and the cells functional biological responses (angiogenesis and permeability) were assessed. We showed that the expression of proteins specific to ECs (ACE+, VWF+), their differentiation (CD31+, CD 133+, CD105+, CD34-), their adhesion properties (ICAM-1+, VCAM-1+, CD62-L+), and their barrier formation (ZO-1+) were all downregulated in tumor-derived ECs. NGS-based differential transcriptome analysis confirmed CD31-lowered expression and pointed to the increase of Ephrin-B2 and SNCAIP, indicative of dedifferentiation. Functional assays confirmed these differences; angiogenesis was impaired while permeability increased in tumor-derived ECs, as further validated by the distinctly enhanced VEGF production in response to hypoxia, reflecting the tumor conditions. This work showed that endothelial cells differed highly significantly, both phenotypically and functionally, in the tumor site as compared to the normal corresponding tissue, thus influencing the tumor microenvironment. |
| first_indexed | 2024-03-10T08:44:01Z |
| format | Article |
| id | doaj.art-893271f877894a658c26e170cb6cc1ca |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T08:44:01Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-893271f877894a658c26e170cb6cc1ca2023-11-22T08:01:44ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-08-012216886210.3390/ijms22168862Distinctive Properties of Endothelial Cells from Tumor and Normal Tissue in Human Breast CancerKinga Wilkus0Klaudia Brodaczewska1Arkadiusz Kajdasz2Claudine Kieda3Laboratory of Molecular Oncology and Innovative Therapies, Military Institute of Medicine, PL-04-141 Warsaw, PolandLaboratory of Molecular Oncology and Innovative Therapies, Military Institute of Medicine, PL-04-141 Warsaw, PolandLaboratory of Human Molecular Genetics, Faculty of Biology, Institute of Molecular Biology and Biotechnology, Adam Mickiewicz University Poznan, 61-614 Poznan, PolandLaboratory of Molecular Oncology and Innovative Therapies, Military Institute of Medicine, PL-04-141 Warsaw, PolandTumor microenvironments shape aggressiveness and are largely maintained by the conditions of angiogenesis formation. Thus, endothelial cells’ (ECs) biological reactions are crucial to understand and control the design of efficient therapies. In this work, we used models of ECs to represent a breast cancer tumor site as well as the same, healthy tissue. Cells characterization was performed at the transcriptome and protein expression levels, and the cells functional biological responses (angiogenesis and permeability) were assessed. We showed that the expression of proteins specific to ECs (ACE+, VWF+), their differentiation (CD31+, CD 133+, CD105+, CD34-), their adhesion properties (ICAM-1+, VCAM-1+, CD62-L+), and their barrier formation (ZO-1+) were all downregulated in tumor-derived ECs. NGS-based differential transcriptome analysis confirmed CD31-lowered expression and pointed to the increase of Ephrin-B2 and SNCAIP, indicative of dedifferentiation. Functional assays confirmed these differences; angiogenesis was impaired while permeability increased in tumor-derived ECs, as further validated by the distinctly enhanced VEGF production in response to hypoxia, reflecting the tumor conditions. This work showed that endothelial cells differed highly significantly, both phenotypically and functionally, in the tumor site as compared to the normal corresponding tissue, thus influencing the tumor microenvironment.https://www.mdpi.com/1422-0067/22/16/8862microenvironmentangiogenesisendothelial cellsbreast cancerorganospecificityvascular dysfunction |
| spellingShingle | Kinga Wilkus Klaudia Brodaczewska Arkadiusz Kajdasz Claudine Kieda Distinctive Properties of Endothelial Cells from Tumor and Normal Tissue in Human Breast Cancer International Journal of Molecular Sciences microenvironment angiogenesis endothelial cells breast cancer organospecificity vascular dysfunction |
| title | Distinctive Properties of Endothelial Cells from Tumor and Normal Tissue in Human Breast Cancer |
| title_full | Distinctive Properties of Endothelial Cells from Tumor and Normal Tissue in Human Breast Cancer |
| title_fullStr | Distinctive Properties of Endothelial Cells from Tumor and Normal Tissue in Human Breast Cancer |
| title_full_unstemmed | Distinctive Properties of Endothelial Cells from Tumor and Normal Tissue in Human Breast Cancer |
| title_short | Distinctive Properties of Endothelial Cells from Tumor and Normal Tissue in Human Breast Cancer |
| title_sort | distinctive properties of endothelial cells from tumor and normal tissue in human breast cancer |
| topic | microenvironment angiogenesis endothelial cells breast cancer organospecificity vascular dysfunction |
| url | https://www.mdpi.com/1422-0067/22/16/8862 |
| work_keys_str_mv | AT kingawilkus distinctivepropertiesofendothelialcellsfromtumorandnormaltissueinhumanbreastcancer AT klaudiabrodaczewska distinctivepropertiesofendothelialcellsfromtumorandnormaltissueinhumanbreastcancer AT arkadiuszkajdasz distinctivepropertiesofendothelialcellsfromtumorandnormaltissueinhumanbreastcancer AT claudinekieda distinctivepropertiesofendothelialcellsfromtumorandnormaltissueinhumanbreastcancer |