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

被引：59

作者：

Dittmer, Angela ^{[1
]}

Hohlfeld, Kristina ^{[1
]}

Luetzkendorf, Jana ^{[2
]}

Mueller, Lutz P. ^{[2
]}

Dittmer, Juergen ^{[1
]}

机构：

[1] Univ Halle Wittenberg, Klin Gynakol, Halle, Saale, Germany

[2] Univ Halle Wittenberg, Klin Innere Med 4, Zentrum Innere Med, Halle, Saale, Germany

来源：

CELLULAR AND MOLECULAR LIFE SCIENCES | 2009年 / 66卷 / 18期

关键词：

MSC; Spheroids; Breast cancer; Migration; ADAM; 10; E-cadherin; HUMAN BONE-MARROW; STROMAL CELLS; TUMOR STROMA; CANCER; BETA; PROTEIN; ANGIOGENESIS; APOPTOSIS; MIGRATION; DELIVERY;

D O I：

10.1007/s00018-009-0089-0

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

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

页码：3053 / 3065

页数：13

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