Human mesenchymal stem cells induce E-cadherin degradation in breast carcinoma spheroids by activating ADAM10.

Autor: Dittmer, Angela, Hohlfeld, Kristina, Lützkendorf, Jana, Müller, Lutz P., Dittmer, Jürgen
Předmět:
Zdroj: Cellular & Molecular Life Sciences; Sep2009, Vol. 66 Issue 18, p3053-3065, 13p, 2 Color Photographs, 3 Diagrams, 3 Graphs
Abstrakt: 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. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index