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

Area of Science:

• Cell Biology
• Cancer Research
• Biotechnology

Background:

• Tetraspanin CD9 is expressed on various cells, including mesenchymal stem cells (MSCs) and cancer cells.
• Exosomal CD9 influences cancer cell migration and metastasis.
• The role of MSC CD9 in cancer cell migration remains unclear.

Purpose of the Study:

• To investigate the effect of MSC CD9 on cancer cell migration.
• To explore the impact of dextran-coated iron oxide nanoparticles (dex-IO NPs) and ionomycin on MSC CD9 expression.
• To elucidate the mechanism by which MSCs influence cancer cell migration.

Main Methods:

• Transwell migration assays were used to assess cancer cell migration.
• Human MSCs (hMSCs) were treated with dex-IO NPs and ionomycin.
• CD9 expression in hMSCs and conditioned media was analyzed.
• CCL21 expression and secretion in hMSCs were measured.
• CD9 silencing was performed in hMSCs.

Main Results:

• Both dex-IO NPs and ionomycin stimulated exosomal CD9 in hMSCs, but hMSCs did not transfer it to melanoma cells.
• Ionomycin-treated hMSC-conditioned media reduced melanoma cell migration.
• Dex-IO NPs decreased, while ionomycin increased, cellular CD9 in hMSCs.
• Ionomycin suppressed CCL21 expression and secretion in hMSCs.
• CD9 silencing confirmed its inhibitory role in CCL21 expression.
• Reduced CCL21 chemoattraction by hMSCs decreased migration of B16F10, A549, and U87MG cancer cells.

Conclusions:

• hMSCs CD9 plays a role in regulating CCL21, affecting cancer metastasis.
• Ionomycin upregulates cellular CD9 in hMSCs, leading to decreased CCL21.
• This mechanism reduces cancer cell migration by lowering chemoattraction.
• The findings suggest a novel pharmaceutical strategy for preventing or treating cancer metastasis.