Dynamic interplay between breast cancer cells and normal endothelium mediates the expression of matrix macromolecules, proteasome activity and functional properties of endothelial cells.

Autor:	Gialeli Ch; Biochemistry, Biochemical Analysis & Matrix Pathobiology Res. Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, 26110 Patras, Greece; Foundation for Research and Technology, Institute of Chemical Engineering Sciences (FORTH/ICE-HT), 26500 Patras, Greece., Viola M; Department of Surgery and Morphological Sciences, University of Insubria, Varese, Italy., Barbouri D; Biochemistry, Biochemical Analysis & Matrix Pathobiology Res. Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, 26110 Patras, Greece; Foundation for Research and Technology, Institute of Chemical Engineering Sciences (FORTH/ICE-HT), 26500 Patras, Greece., Kletsas D; Laboratory of Cell Proliferation and Ageing, Institute of Biology, National Center of Scientific Research 'Demokritos', Athens, Greece., Passi A; Department of Surgery and Morphological Sciences, University of Insubria, Varese, Italy., Karamanos NK; Biochemistry, Biochemical Analysis & Matrix Pathobiology Res. Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, 26110 Patras, Greece; Foundation for Research and Technology, Institute of Chemical Engineering Sciences (FORTH/ICE-HT), 26500 Patras, Greece. Electronic address: n.k.karamanos@upatras.gr.
Jazyk:	angličtina
Zdroj:	Biochimica et biophysica acta [Biochim Biophys Acta] 2014 Aug; Vol. 1840 (8), pp. 2549-59. Date of Electronic Publication: 2014 Feb 26.
DOI:	10.1016/j.bbagen.2014.02.019
Abstrakt:	Background: Breast cancer-endothelium interactions provide regulatory signals facilitating tumor progression. The endothelial cells have so far been mainly viewed in the context of tumor perfusion and relatively little is known regarding the effects of such paracrine interactions on the expression of extracellular matrix (ECM), proteasome activity and properties of endothelial cells. Methods: To address the effects of breast cancer cell (BCC) lines MDA-MB-231 and MCF-7 on the endothelial cells, two cell culture models were utilized; one involves endothelial cell culture in the presence of BCCs-derived conditioned media (CM) and the other co-culture of both cell populations in a Transwell system. Real-time PCR was utilized to evaluate gene expression, an immunofluorescence assay for proteasome activity, and functional assays (migration, adhesion and invasion) and immunofluorescence microscopy for cell integrity and properties. Results: BCC-CM decreases the cell migration of HUVEC. Adhesion and invasion of BCCs are favored by HUVEC and HUVEC-CM. HA levels and the expression of CD44 and HA synthase-2 by HUVEC are substantially upregulated in both cell culture approaches. Adhesion molecules, ICAM-1 and VCAM-1, are also highly upregulated, whereas MT1-MMP and MMP-2 expressions are significantly downregulated in both culture systems. Notably, the expression and activity of the proteasome β5 subunit are increased, especially by the action of MDA-MB-231-CM on HUVEC. Conclusions and General Significance: BCCs significantly alter the expression of matrix macromolecules, proteasome activity and functional properties of endothelial cells. Deep understanding of such paracrine interactions will help to design novel drugs targeting breast cancer at the ECM level. This article is part of a Special Issue entitled Matrix-mediated cell behaviour and properties. (Copyright © 2014 Elsevier B.V. All rights reserved.)
Databáze:	MEDLINE
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