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- Title
Human mesenchymal stem cells induce E-cadherin degradation in breast carcinoma spheroids by activating ADAM10.
- Authors
Dittmer, Angela; Hohlfeld, Kristina; Lützkendorf, Jana; Müller, Lutz P.; Dittmer, Jürgen
- Abstract
Mesenchymal stem cells (MSCs) have been shown to communicate with tumor cells. We analyzed the effect of human MSCs (hMSCs) on breast cancer cells in three-dimensional cultures. By using GFP expression and immunohistochemistry, we show that hMSCs invade 3D breast cancer cell aggregates. hMSCs caused breast cancer spheroids to become disorganized which was accompanied by a disruption of cell–cell adhesion, E-cadherin cleavage, and nuclear translocation of E-cadherin, but not by epithelial/mesenchymal transition or by an increase in ERK1/2 activity. In addition, hMSCs enhanced the motility of breast cancer cells. Inhibition of ADAM10 (a disintegrin and metalloprotease 10), known to cleave E-cadherin, prevented both hMSC-mediated E-cadherin cleavage and enhanced migration. Our data suggest that hMSCs interfere with cell–cell adhesion and enhance migration of breast cancer cells by activating ADAM10.
- Subjects
STEM cells; CADHERINS; BREAST cancer; CANCER cells; CELL migration
- Publication
Cellular & Molecular Life Sciences, 2009, Vol 66, Issue 18, p3053
- ISSN
1420-682X
- Publication type
Article
- DOI
10.1007/s00018-009-0089-0