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

被引:0
作者
Angela Dittmer
Kristina Hohlfeld
Jana Lützkendorf
Lutz P. Müller
Jürgen Dittmer
机构
[1] Universität Halle,Klinik für Gynäkologie
[2] Universität Halle,Zentrum für Innere Medizin, Klinik für Innere Medizin IV
来源
Cellular and Molecular Life Sciences | 2009年 / 66卷
关键词
MSC; Spheroids; Breast cancer; Migration; ADAM 10; E-cadherin;
D O I
暂无
中图分类号
学科分类号
摘要
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.
引用
收藏
页码:3053 / 3065
页数:12
相关论文
共 235 条
[11]  
Evan G(2005)Stromal fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated SDF-1/CXCL12 secretion Cell 121 335-348
[12]  
Dominici M(2006)Immune modulation by mesenchymal stem cells Exp Cell Res 312 2169-2179
[13]  
Le Blanc K(2006)Human mesenchymal stem cells exert potent antitumorigenic effects in a model of Kaposi’s sarcoma J Exp Med 203 1235-1247
[14]  
Mueller I(2008)The ADAM metalloproteinases Mol Aspects Med 29 258-289
[15]  
Slaper-Cortenbach I(2005)ADAM10 mediates E-cadherin shedding and regulates epithelial cell–cell adhesion, migration, and beta-catenin translocation Proc Natl Acad Sci USA 102 9182-9187
[16]  
Marini F(2003)In vitro propagation and transcriptional profiling of human mammary stem/progenitor cells Genes Dev 17 1253-1270
[17]  
Krause D(2008)PTHrP promotes homotypic aggregation of breast cancer cells in three-dimensional cultures Cancer Lett 260 56-61
[18]  
Deans R(2006)Presence of mesenchymal stem cells in human bone marrow after exposure to chemotherapy: evidence of resistance to apoptosis induction Stem Cells 24 2753-2765
[19]  
Keating A(1998)High-titer human immunodeficiency virus type 1-based vector systems for gene delivery into nondividing cells J Virol 72 8873-8883
[20]  
Prockop D(2002)Germline transmission and tissue-specific expression of transgenes delivered by lentiviral vectors Science 295 868-872