title: Human mesenchymal stem cells induce E-cadherin degradation in breast carcinoma spheroids by activating ADAM10.
abstract: 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.
authors: Klinik für Gynäkologie, Universität Halle, Halle (Saale), Germany.
authors: Angela
authors: A
authors: Dittmer
authors: Kristina
authors: K
authors: Hohlfeld
authors: Jana
authors: J
authors: Lützkendorf
authors: Lutz P
authors: LP
authors: Müller
authors: Jürgen
authors: J
authors: Dittmer
mesh_terms: 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
chemical_list: 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