Next Article in Journal
Efficient Chitosan/Nitrogen-Doped Reduced Graphene Oxide Composite Membranes for Direct Alkaline Ethanol Fuel Cells
Next Article in Special Issue
Involvement of IL-4, IL-13 and Their Receptors in Pancreatic Cancer
Previous Article in Journal
Understanding Viral Infection Mechanisms and Patient Symptoms for the Development of COVID-19 Therapeutics
Previous Article in Special Issue
Is the C-C Motif Ligand 2–C-C Chemokine Receptor 2 Axis a Promising Target for Cancer Therapy and Diagnosis?
Article

CD9 Upregulation-Decreased CCL21 Secretion in Mesenchymal Stem Cells Reduces Cancer Cell Migration

1
Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Miaoli 35053, Taiwan
2
Department of Laboratory Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei 100225, Taiwan
3
Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei 100225, Taiwan
*
Author to whom correspondence should be addressed.
Academic Editor: Mohd W. Nasser
Int. J. Mol. Sci. 2021, 22(4), 1738; https://doi.org/10.3390/ijms22041738
Received: 30 December 2020 / Revised: 30 January 2021 / Accepted: 5 February 2021 / Published: 9 February 2021
(This article belongs to the Special Issue Cytokines/Chemokines in Cancer Metastasis)
Tetraspanin CD9 is widely expressed on various cell types, such as cancer cells and mesenchymal stem cells (MSCs), and/or cell-released exosomes. It has been reported that exosomal CD9 plays an important role in intercellular communications involved in cancer cell migration and metastasis. However, reports on the effect of the CD9 of MSCs or MSC-derived exosomes on cancer cell migration are still lacking. In this study, using a transwell migration assay, we found that both dextran-coated iron oxide nanoparticles (dex-IO NPs) and ionomycin stimulated exosomal CD9 expression in human MSCs (hMSCs); however, hMSCs could not deliver them to melanoma cells to affect cell migration. Interestingly, a reduced migration of melanoma cell line was observed when the ionomycin-incubated hMSC-conditioned media but not dex-IO NP-labeled hMSC-conditioned media were in the bottom chamber. In addition, we found that dex-IO NPs decreased cellular CD9 expression in hMSCs but ionomycin increased this. Simultaneously, we found that ionomycin suppressed the expression and secretion of the chemokine CCL21 in hMSCs. The silencing of CD9 demonstrated an inhibitory role of cellular CD9 in CCL21 expression in hMSCs, suggesting that ionomycin could upregulate cellular CD9 to decrease CCL21 expression and secretion of hMSCs, which would reduce the migration of B16F10, A549 and U87MG cancer cell lines due to chemoattraction reduction of CCL21. The present study not only highlights the important role of bone marrow-derived hMSCs’ CD9-mediated CCL21 regulation in cancer bone metastasis but also suggests a new distinct pharmaceutical strategy for prevention or/and therapy of cancer metastasis. View Full-Text
Keywords: cancer cell migration; mesenchymal stem cells; CD9; CCL21 chemokine; ionomycin; nanoparticles cancer cell migration; mesenchymal stem cells; CD9; CCL21 chemokine; ionomycin; nanoparticles
Show Figures

Figure 1

MDPI and ACS Style

Hsieh, C.-C.; Hsu, S.-C.; Yao, M.; Huang, D.-M. CD9 Upregulation-Decreased CCL21 Secretion in Mesenchymal Stem Cells Reduces Cancer Cell Migration. Int. J. Mol. Sci. 2021, 22, 1738. https://doi.org/10.3390/ijms22041738

AMA Style

Hsieh C-C, Hsu S-C, Yao M, Huang D-M. CD9 Upregulation-Decreased CCL21 Secretion in Mesenchymal Stem Cells Reduces Cancer Cell Migration. International Journal of Molecular Sciences. 2021; 22(4):1738. https://doi.org/10.3390/ijms22041738

Chicago/Turabian Style

Hsieh, Chia-Chu, Szu-Chun Hsu, Ming Yao, and Dong-Ming Huang. 2021. "CD9 Upregulation-Decreased CCL21 Secretion in Mesenchymal Stem Cells Reduces Cancer Cell Migration" International Journal of Molecular Sciences 22, no. 4: 1738. https://doi.org/10.3390/ijms22041738

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop