期刊
CELLULAR AND MOLECULAR LIFE SCIENCES
卷 66, 期 18, 页码 3053-3065出版社
SPRINGER BASEL AG
DOI: 10.1007/s00018-009-0089-0
关键词
MSC; Spheroids; Breast cancer; Migration; ADAM 10; E-cadherin
资金
- Land Sachsen-Anhalt (Germany) [FKZ SI/08]
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.
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