CD9 Upregulation-Decreased CCL21 Secretion in Mesenchymal Stem Cells Reduces Cancer Cell Migration
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,...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-02-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/22/4/1738 |
| _version_ | 1797412265659465728 |
|---|---|
| author | Chia-Chu Hsieh Szu-Chun Hsu Ming Yao Dong-Ming Huang |
| author_facet | Chia-Chu Hsieh Szu-Chun Hsu Ming Yao Dong-Ming Huang |
| author_sort | Chia-Chu Hsieh |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T05:00:30Z |
| format | Article |
| id | doaj.art-d70bbbe10ae64fb3b58224557dca2f3f |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T05:00:30Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-d70bbbe10ae64fb3b58224557dca2f3f2023-12-03T13:01:29ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-02-01224173810.3390/ijms22041738CD9 Upregulation-Decreased CCL21 Secretion in Mesenchymal Stem Cells Reduces Cancer Cell MigrationChia-Chu Hsieh0Szu-Chun Hsu1Ming Yao2Dong-Ming Huang3Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Miaoli 35053, TaiwanDepartment of Laboratory Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei 100225, TaiwanDepartment of Internal Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei 100225, TaiwanInstitute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Miaoli 35053, TaiwanTetraspanin 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.https://www.mdpi.com/1422-0067/22/4/1738cancer cell migrationmesenchymal stem cellsCD9CCL21 chemokineionomycinnanoparticles |
| spellingShingle | Chia-Chu Hsieh Szu-Chun Hsu Ming Yao Dong-Ming Huang CD9 Upregulation-Decreased CCL21 Secretion in Mesenchymal Stem Cells Reduces Cancer Cell Migration International Journal of Molecular Sciences cancer cell migration mesenchymal stem cells CD9 CCL21 chemokine ionomycin nanoparticles |
| title | CD9 Upregulation-Decreased CCL21 Secretion in Mesenchymal Stem Cells Reduces Cancer Cell Migration |
| title_full | CD9 Upregulation-Decreased CCL21 Secretion in Mesenchymal Stem Cells Reduces Cancer Cell Migration |
| title_fullStr | CD9 Upregulation-Decreased CCL21 Secretion in Mesenchymal Stem Cells Reduces Cancer Cell Migration |
| title_full_unstemmed | CD9 Upregulation-Decreased CCL21 Secretion in Mesenchymal Stem Cells Reduces Cancer Cell Migration |
| title_short | CD9 Upregulation-Decreased CCL21 Secretion in Mesenchymal Stem Cells Reduces Cancer Cell Migration |
| title_sort | cd9 upregulation decreased ccl21 secretion in mesenchymal stem cells reduces cancer cell migration |
| topic | cancer cell migration mesenchymal stem cells CD9 CCL21 chemokine ionomycin nanoparticles |
| url | https://www.mdpi.com/1422-0067/22/4/1738 |
| work_keys_str_mv | AT chiachuhsieh cd9upregulationdecreasedccl21secretioninmesenchymalstemcellsreducescancercellmigration AT szuchunhsu cd9upregulationdecreasedccl21secretioninmesenchymalstemcellsreducescancercellmigration AT mingyao cd9upregulationdecreasedccl21secretioninmesenchymalstemcellsreducescancercellmigration AT dongminghuang cd9upregulationdecreasedccl21secretioninmesenchymalstemcellsreducescancercellmigration |