scholarly journals Distinctive Properties of Endothelial Cells from Tumor and Normal Tissue in Human Breast Cancer

2021 ◽  
Vol 22 (16) ◽  
pp. 8862
Author(s):  
Kinga Wilkus ◽  
Klaudia Brodaczewska ◽  
Arkadiusz Kajdasz ◽  
Claudine Kieda
Keyword(s):  
Breast Cancer ◽  
Endothelial Cells ◽  
Tumor Site ◽  
Human Breast ◽  
Adhesion Properties ◽  
Tumor Microenvironments ◽  
Biological Responses ◽  
Barrier Formation ◽  
Cancer Tumor ◽  
And Control

Tumor microenvironments shapes 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.

scholarly journals Systemic Sclerosis-Endothelial Cell Antiangiogenic Pentraxin 3 and Matrix Metalloprotease 12 Control Human Breast Cancer Tumor Vascularization and Development in Mice

Neoplasia ◽  
2009 ◽  
Vol 11 (10) ◽  
pp. 1106-1115 ◽  
Author(s):  
Francesca Margheri ◽  
Simona Serratì ◽  
Andrea Lapucci ◽  
Chillà Anastasia ◽  
Betti Giusti ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Systemic Sclerosis ◽  
Endothelial Cell ◽  
Human Breast Cancer ◽  
Pentraxin 3 ◽  
Matrix Metalloprotease ◽  
Human Breast ◽  
Tumor Vascularization ◽  
Cancer Tumor

The radiosensitivity of endothelial cells isolated from human breast cancer and normal tissue in vitro

2012 ◽  
Vol 84 (2) ◽  
pp. 140-148 ◽  
Author(s):  
Moon-Taek Park ◽  
Eun-Taex Oh ◽  
Min-Jeong Song ◽  
Woo-Jean Kim ◽  
Young Up Cho ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endothelial Cells ◽  
Human Breast Cancer ◽  
Normal Tissue ◽  
Human Breast

Study the Effect of Anticancer Drugs on Human Breast Cancer Cells Using Three Dimensional Silicon Microstructures

2008 ◽  
Author(s):  
Mehdi Nikkhah ◽  
Jeannine S. Strobl ◽  
Masoud Agah
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Anticancer Drugs ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Trichostatin A ◽  
Three Dimensional ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
Adhesion Properties

In this paper we report development of three dimensional silicon microenvironments in order to test the morphological changes and adhesion properties of human breast cancer cells after treatment with different anticancer drugs such as Trichostatin A (TSA), suberoylanilide hydroxamic acid (SAHA) and Scriptaid. Our results indicate that the cancer cells reorganize their cytoskeleton structure after treatment with TSA and Scriptaid. However, SAHA does not change the behavior of the cells inside the three dimensional microstructures while TSA and Scriptaid evoked striking changes in the cells morphology. TSA and Scriptaid drugs cause the cells to stretch inside the isotropic microchambers to avoid contact with curved sidewalls in contrast to their originally rounded shape. The proposed microstructures can be used to evaluate mechanical properties and the pathological grade of various cancer cell lines after different conditions i.e. drug exposure.

scholarly journals Damage to cardiac vasculature may be associated with breast cancer treatment-induced cardiotoxicity

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Rebecca K. Hoffman ◽  
Bang-Jin Kim ◽  
Payal D. Shah ◽  
Joseph Carver ◽  
Bonnie Ky ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endothelial Cells ◽  
Ejection Fraction ◽  
Cancer Treatment ◽  
Human Breast Cancer ◽  
Breast Cancer Treatment ◽  
Human Breast ◽  
Lv Mass ◽  
Lv Ejection Fraction

Abstract Background Breast cancer is the most common female cancer worldwide. Effective therapies including doxorubicin and trastuzumab have improved survival, but are associated with a substantial risk of cardiovascular disease. Mechanisms underlying cancer treatment-induced cardiotoxicity (CTC) are poorly understood and have largely focused on cardiomyocyte damage, although other cellular populations in the heart such as the cardiac endothelium, may play an important role in cardiac damage. We treated a breast tumor-bearing mouse model with doxorubicin and trastuzumab to investigate the role of the cardiac endothelium in the development of CTC. Methods Immune compromised mice were inoculated in the 4th mammary fat pad with human breast cancer cells overexpressing HER2 (BT474). When tumors were palpable, mice were treated weekly with doxorubicin (5 mg/kg) and trastuzumab (4 mg/kg). The cardiac phenotype of mice was assessed by echocardiography and histological evaluation of the heart. Cardiac vascular damage was assayed by in vivo permeability assays and primary cultures of murine cardiac endothelial cells were used to assay doxorubicin toxicity in vitro. Results The growth of BT474 breast tumors in Balb/c Nude mice was suppressed upon treatment with doxorubicin and trastuzumab. Mice treated for 4 months with doxorubicin and trastuzumab maintained body weights, but demonstrated an echocardiographic phenotype consistent with preserved left ventricular (LV) ejection fraction, decreased LV mass and increased filling pressures (E/e’). Histological staining with Masson’s trichrome and Picrosirius red showed extensive fibrosis and increased collagen deposition in the ventricular myocardium surrounding blood vessels of treated mice compared to untreated mice. Evans blue permeability assays demonstrated increased cardiac vasculature permeability while primary cardiac endothelial cells exposed to doxorubicin in vitro showed increased cell death as compared to lung or liver endothelial cells. Conclusions An orthotopic mouse model of human breast cancer in Nude mice treated with doxorubicin and trastuzumab resulted in a cardiac vascular defect accompanied by preserved LV ejection fraction, decreased LV mass, suggesting mild diastolic dysfunction and cardiac remodeling consistent with subclinical cardiotoxicity. Our data suggest that cardiac endothelium is more sensitive to doxorubicin therapy as compared to other organ endothelium and cardiac endothelial damage may correlate with breast cancer treatment-induced cardiotoxicity.

CD45-CD34+ Endothelial Progenitor Cells (EPCs) from Human Adipose Tissue Promote Tumor Growth and Metastases

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2208-2208
Author(s):  
Patrizia Mancuso ◽  
Ines Martin Padura ◽  
Giuliana Gregato ◽  
Paola Marighetti ◽  
Angelica Calleri ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Marrow ◽  
Endothelial Cells ◽  
Adipose Tissue ◽  
Breast Reconstruction ◽  
Progenitor Cells ◽  
Human Breast Cancer ◽  
Human Adipose Tissue ◽  
Human Breast ◽  
Cd34 Cells

Abstract Abstract 2208 A catalytic role has been proposed in neoplastic angiogenesis and cancer progression for bone marrow-derived endothelial progenitor cells (EPCs). However, in preclinical and clinical studies the quantitative role of marrow-derived EPCs in cancer vascularization was found to be extremely variable. Adipose tissue represents an attractive source of autologous adult stem cells due to its abundance and surgical accessibility. Lipotransfer aspirates (LAs) from patients undergoing breast reconstruction after breast cancer surgery were analyzed by six colors flow cytometry and tissue culture. After collagenase digestion, cells were stained with the nuclear binding antigen Syto16 and 7-AAD and with CD34, CD45, CD133, CD31, CD140b, CD105, CD90, CD44, CD13, CD144, CD10, CD29, CD109, CD117, CD146,CD16, CD11c, CD14, CD38, CXCR4, VEGFR-1, VEGFR-2, VEGFR-3, Tie-2. The absolute count of CD45-CD34+ cells was obtained using reference beads in Trucount tubes (BD, Mountain View, CA). LAs were found to contain a large amount of CD45-CD34+ cells fulfilling the most recent criteria for EPC identification. These CD45-CD34+ cells included two subpopulations: CD45-CD34++ CD13+ CD140b+ CD44+ CD90++ cells and CD45-CD34+ CD31+CD105+ cells. We found in the adipose tissue about 263 fold more CD45-CD34+ EPCs/mL when compared to the bone marrow. In particular, the median of CD45-CD34+CD31- cells/mL was 181,046 (range 35,970–465,357), and the median of CD45-CD34+CD31+ cells/mL was 76,946 (range13,982-191,287). When compared to marrow-derived CD34+ cells, purified CD45-CD34+ adipose cells expressed similar levels of stemness-related genes such as NANOG, SOX2, Lin28 and significantly increased levels of angiogenesis-related genes such as CD144, VEGFR2, ALK-1. In vitro, CD45-CD34+ cells generated mature endothelial cells and capillary tubes as well as mature mesenchymal cells. When coinjected with triple negative human breast cancer MDA-MB-436 and HCC1937 cells in the mammary fat of a murine model of human breast cancer, purified CD45-CD34+ cells significantly increased tumor growth, and immunohistochemistry studies demonstrated the presence of human CD31+, CD34+, CD105+ endothelial cells lining the vessels of orthotopic breast cancers growing in mice co-injected with human adipose tissue-derived CD45-CD34+ cells. Moreover, in a mouse model of breast cancer metastatization we found an increased number of lung and axillary lymph node metastases when purified CD34+ WAT cells were injected into the third mammary fat pad after the primary tumor resection. In conclusion our data demonstrate that the phenotype of adipose derived EPCs is consistent with that reported for both bone marrow and circulating EPCs, but their frequency in adipose tissue is more than 250 fold higher. Further studies are ongoing to clarify what cell populations residing in the adipose tissue can be used safely for breast reconstruction and what are at risk for supporting the growth of otherwise quiescent cancer cells still resident after surgery. Disclosures: No relevant conflicts of interest to declare.

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