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Endoglin expression in metastatic breast cancer cells enhances their invasive phenotype.

Authors :
Oxmann D
Held-Feindt J
Stark AM
Hattermann K
Yoneda T
Mentlein R
Source :
Oncogene [Oncogene] 2008 Jun 05; Vol. 27 (25), pp. 3567-75. Date of Electronic Publication: 2008 Jan 28.
Publication Year :
2008

Abstract

Endoglin is a cell-surface adhesion protein as well as a coreceptor for transforming growth factor-beta (TGF-beta). It is located on endothelial and few other cells, but also found on certain tumor cells. Brain metastatic breast tumor cells derived from the MDA-MB-231 cell line heavily express endoglin in contrast to the corresponding parental ones. To clarify whether this determines their invasive phenotype, we compared their biological properties with endoglin-silenced brain-metastatic cells, low-expressing parental cells and these transfected with L- and S-endoglins, isoforms transducing or lacking TGF-beta signals. All L-endoglin-overexpressing cells were characterized by numerous invadopodia where endoglin was preferentially localized. Endoglin-expression resulted in elevated levels of the matrix metalloproteinases (MMP-1 and MMP-19) and downregulation of the plasminogen activator inhibitor-1. In Boyden-chamber and wound-healing assays, endoglin-overexpressing cells showed a considerably higher migration and chemotaxis to TGF-beta. In 3D spheroid confrontation assays between breast tumor cells and TGF-beta-secreting glioma cells, high L-endoglin-expressing cells invaded into the glioma-spheroids whereas low-endoglin-expressing cells dissociated in the culture; invasion was blocked by TGF-beta antibodies. In contrast to parental cells, endoglin-overexpressing cells invaded deeply into mouse brain slices. Thus, endoglin expression on tumor cells enhances their invasive character by formation of invadopodia, extracellular proteolysis, chemotaxis and migration.

Details

Language :
English
ISSN :
1476-5594
Volume :
27
Issue :
25
Database :
MEDLINE
Journal :
Oncogene
Publication Type :
Academic Journal
Accession number :
18223685
Full Text :
https://doi.org/10.1038/sj.onc.1211025