Tumor Microenvironment Changing through Application of MicroRNA-34a Related Mesenchymal Stem Cells Conditioned Medium: Modulation of Breast Cancer Cells toward Non-aggressive Behavior
Conditioned medium (CM) derived from mesenchymal stem cells (MSCs) contains bioactive molecules including microRNAs (miRs) that could be a potential tool for controlling cancer cells' behavior. Due to the properties of CM, this study assesses the effects of miR-34a related MSC-CM on tumor behavior through the evaluation of migration, invasion, apoptosis, and PDL1 expression in breast cancer cell lines.
The miR-34a overexpression vector or scramble control was produced using lentiviral vectors, DNA cloning, and the transfection of the HEK-293T cell line. It was then transduced into human adipose-derived mesenchymal stem cells (hAD-MSCs). MSC-CMs were collected and added onto MDA-MB-231 cell lines. The functional evaluations were performed by transwell, wound healing, and Annexin V/PI methods on the treated MDA-MB-231 cell lines. The PDL1 expression was also assessed by Real-time PCR and western blot.
The findings of this study showed that ectopic miR‑34a expression was significantly upregulated in manipulated hASC with miR-34a (p<0.0001). Treatment of MDA-MB-231 cell line with miR-34a-hAD-MSC-CM, scramble-hAD-MSC-CM, or hAD-MSC-CM displayed not only a reduction in the number of migrated or invaded cells (p=0.01) but also an increase in the apoptotic cells in the test group (p=0.02) when compared to the control groups. It also showed down-regulation in the gene (p=0.05) and protein expression levels of PDL1 in the test group.
The results of the present study showed that simultaneous application of miR-34a and MSC-CM can be considered as a new method for changing the cancerous microenvironment; and therefore, as a potential strategy in breast cancer therapy.
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|Issue||Vol 20 No 2 (2021)|
|Adipose-derived mesenchymal stem cells Breast neoplasms Conditioned medium MIRN34 microRNA|
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