N-cadherin mediates the migration of bone marrow-derived mesenchymal stem cells toward breast tumor cells
| Autor: | Sanghyuk Choi, Wootak Kim, Jinyeong Yu, Ki-Sook Park |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Cell signaling Pyridines Receptor Transforming Growth Factor-beta Type I Medicine (miscellaneous) Breast Neoplasms Real-Time Polymerase Chain Reaction p38 Mitogen-Activated Protein Kinases Adherens junction 03 medical and health sciences 0302 clinical medicine bone marrow-derived mesenchymal stem cell Antigens CD Cell Movement Transforming Growth Factor beta Cell Line Tumor medicine Cell Adhesion Tumor Microenvironment Humans Benzodioxoles RNA Small Interfering Pharmacology Toxicology and Pharmaceutics (miscellaneous) Protein kinase B N-cadherin Smad4 Protein Tumor microenvironment Gene knockdown Cadherin Chemistry breast tumor Mesenchymal stem cell Imidazoles TGF-β Mesenchymal Stem Cells Cadherins Immunohistochemistry 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Culture Media Conditioned Cancer research Female Bone marrow Proto-Oncogene Proteins c-akt Research Paper Signal Transduction |
| Zdroj: | Theranostics |
| ISSN: | 1838-7640 |
| Popis: | Rationale: Bone marrow-derived mesenchymal stem cells (BM-MSCs) recruited into breast tumors regulate the behavior of tumor cells via various mechanisms and affect clinical outcomes. Although signaling molecules, such as transforming growth factor β (TGF-β), are known to transmit signals between BM-MSCs and breast tumor cells for recruiting BM-MSCs, it is unclear which specific intrinsic molecules involved in cell motility mediate the migration of BM-MSCs into breast tumor. It is also unclear as to how specific intrinsic molecules contribute to the migration. Methods: Conditioned medium (CM) from breast tumor cells (MCF-7 and MDA-MB-231) that simulates breast tumor secreting TGF-β was used to examine the migration of BM-MSCs into breast tumors. A three-dimensional migration assay was performed to investigate the collective migration of BM-MSCs, maintaining cell-cell adhesion, toward breast tumor cells. Results: N-cadherin formed adherens junction-like structures on the intercellular borders of BM-MSCs, and TGF-β increased the expression of N-cadherin on these borders. Knockdown of Smad4 impaired the TGF-β-mediated increase in N-cadherin expression in BM-MSCs, but inhibitors of non-canonical TGF-β pathways, such as extracellular signal-regulated kinases, Akt, and p38, did not affect it. siRNA-mediated knockdown of N-cadherin and Smad4 impaired the migration of BM-MSCs in response to TGF-β. Conditioned medium from breast tumor cells also enhanced the expression of N-cadherin in BM-MSCs, but inactivation of TGF-β type 1 receptor (TGFBR1) with SB505124 and TGFBR1 knockdown abolished the increase in N-cadherin expression. BM-MSCs collectively migrated toward CM from MDA-MB-231 in vitro while maintaining cell-cell adhesion through N-cadherin. Knockdown of N-cadherin abolished the migration of BM-MSCs toward the CM from breast tumor cells. Conclusion: In the present study, we identified N-cadherin, an intrinsic transmembrane molecule in adherens junction-like structures, on BM-MSCs as a mediator for the migration of these cells toward breast tumor. The expression of N-cadherin increases on the intercellular borders of BM-MSCs through the TGF-β canonical signaling and they collectively migrate in response to breast tumor cells expressing TGF-β via N-cadherin-dependent cell-cell adhesion. We, herein, introduce a novel promising strategy for controlling and re-engineering the breast tumor microenvironment. |
| Databáze: | OpenAIRE |
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