Human mesenchymal stem cells induce E-cadherin degradation in breast carcinoma spheroids by activating ADAM10.
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.
Dittmer
Angela
A
Klinik für Gynäkologie, Universität Halle, Halle (Saale), Germany.
Hohlfeld
Kristina
K
Lützkendorf
Jana
J
Müller
Lutz P
LP
Dittmer
Jürgen
J
D051722:ADAM Proteins / Q000378:metabolism / Q000502:physiology*; D000072197:ADAM10 Protein; D021581:Active Transport, Cell Nucleus; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism / Q000502:physiology*; D001943:Breast Neoplasms / Q000473:pathology*; D015820:Cadherins / Q000378:metabolism*; D002448:Cell Adhesion; D002465:Cell Movement; D018920:Coculture Techniques; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology*; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3; D014407:Tumor Cells, Cultured
D015820:Cadherins; D008565:Membrane Proteins; D048052:Mitogen-Activated Protein Kinase 3; D053829:Amyloid Precursor Protein Secretases; D051722:ADAM Proteins; D000072197:ADAM10 Protein; C491236:ADAM10 protein, human