Endothelial cells stimulate growth of normal and cancerous breast epithelial cells in 3D culture

被引:44
作者
Ingthorsson S. [1 ]
Sigurdsson V. [1 ]
Fridriksdottir A.J.R. [2 ]
Jonasson J.G. [3 ]
Kjartansson J. [4 ]
Magnusson M.K. [1 ,5 ]
Gudjonsson T. [1 ]
机构
[1] Department of Anatomy, University of Iceland, University Hospital, Reykjavík, (101)
[2] Department of Cellular and Molecular Medicine, Faculty of Health Science, Copenhagen University, Copenhagen, (2200)
[3] Department of Pathology, Landspitali, University Hospital, Reykjavik
[4] St. Josefs Hospital, Hafnarfjördur, (220)
[5] Department of Pharmacology and Toxicology, Faculty of Medicine, University of Iceland, Reykjavík, (101)
关键词
Colony Size; Myoepithelial Cell; Breast Epithelial Cell; Cloning Efficiency; Luminal Epithelial Cell;
D O I
10.1186/1756-0500-3-184
中图分类号
学科分类号
摘要
Background. Epithelial-stromal interaction provides regulatory signals that maintain correct histoarchitecture and homeostasis in the normal breast and facilitates tumor progression in breast cancer. However, research on the regulatory role of the endothelial component in the normal and malignant breast gland has largely been neglected. The aim of the study was to investigate the effects of endothelial cells on growth and differentiation of human breast epithelial cells in a three-dimensional (3D) co-culture assay. Methods. Breast luminal and myoepithelial cells and endothelial cells were isolated from reduction mammoplasties. Primary cells and established normal and malignant breast cell lines were embedded in reconstituted basement membrane in direct co-culture with endothelial cells and by separation of Transwell filters. Morphogenic and phenotypic profiles of co-cultures was evaluated by phase contrast microscopy, immunostaining and confocal microscopy. Results. In co-culture, endothelial cells stimulate proliferation of both luminal- and myoepithelial cells. Furthermore, endothelial cells induce a subpopulation of luminal epithelial cells to form large acini/ducts with a large and clear lumen. Endothelial cells also stimulate growth and cloning efficiency of normal and malignant breast epithelial cell lines. Transwell and gradient co-culture studies show that endothelial derived effects are mediated - at least partially - by soluble factors. Conclusion. Breast endothelial cells - beside their role in transporting nutrients and oxygen to tissues - are vital component of the epithelial microenvironment in the breast and provide proliferative signals to the normal and malignant breast epithelium. These growth promoting effects of endothelial cells should be taken into consideration in breast cancer biology. © 2010 Gudjonsson et al; licensee BioMed Central Ltd.
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共 38 条
[1]  
Ronnov-Jessen L., Petersen O.W., Bissell M.J., Cellular changes involved in conversion of normal to malignant breast: Importance of the stromal reaction, Physiol Rev, 76, 1, pp. 69-125, (1996)
[2]  
Parmar H., Cunha G.R., Epithelial-stromal interactions in the mouse and human mammary gland in vivo, Endocrine-related Cancer, 11, 3, pp. 437-458, (2004)
[3]  
Shekhar M.P., Pauley R., Heppner G., Host microenvironment in breast cancer development: Extracellular matrix-stromal cell contribution to neoplastic phenotype of epithelial cells in the breast, Breast Cancer Res, 5, 3, pp. 130-135, (2003)
[4]  
Ronnov-Jessen L., Bissell M.J., Breast cancer by proxy: Can the microenvironment be both the cause and consequence?, Trends Mol Med, 15, 1, pp. 5-13, (2009)
[5]  
Briand P., Nielsen K.V., Madsen M.W., Petersen O.W., Trisomy 7p and malignant transformation of human breast epithelial cells following epidermal growth factor withdrawal, Cancer Res, 56, 9, pp. 2039-2044, (1996)
[6]  
Gudjonsson T., The Myoepithelial Cell: Cellular Origin and Heterotypic Signalling in Breast Morphogenesis and Neoplasia, (2002)
[7]  
Ronnov-Jessen L., Petersen O.W., Koteliansky V.E., Bissell M.J., The origin of the myofibroblasts in breast cancer. Recapitulation of tumor environment in culture unravels diversity and implicates converted fibroblasts and recruited smooth muscle cells, J Clin Invest, 95, 2, pp. 859-873, (1995)
[8]  
Boulanger C.A., Mack D.L., Booth B.W., Smith G.H., Interaction with the mammary microenvironment redirects spermatogenic cell fate in vivo, Proc Natl Acad Sci USA, 104, 10, pp. 3871-3876, (2007)
[9]  
Booth B.W., Mack D.L., Androutsellis-Theotokis A., McKay R.D., Boulanger C.A., Smith G.H., The mammary microenvironment alters the differentiation repertoire of neural stem cells, Proc Natl Acad Sci USA, 105, 39, pp. 14891-14896, (2008)
[10]  
Petersen O.W., Ronnov-Jessen L., Weaver V.M., Bissell M.J., Differentiation and cancer in the mammary gland: Shedding light on an old dichotomy, Adv Cancer Res, 75, pp. 135-161, (1998)