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 mir34a related msccm on tumor behavior through the evaluation of migration, invasion, apoptosis, and pdl1 expression in breast cancer cell lines.the mir34a overexpression vector or scramble control was produced using lentiviral vectors, dna cloning, and the transfection of the hek293t cell line. it was then transduced into human adiposederived mesenchymal stem cells (hadmscs). msccms were collected and added onto mdamb231 cell lines. the functional evaluations were performed by transwell, wound healing, and annexin v/pi methods on the treated mdamb231 cell lines. the pdl1 expression was also assessed by realtime pcr and western blot.the findings of this study showed that ectopic mir‑34a expression was significantly upregulated in manipulated hasc with mir34a (p<0.0001). treatment of mdamb231 cell line with mir34ahadmsccm, scramblehadmsccm, or hadmsccm 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 downregulation 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 mir34a and msccm can be considered as a new method for changing the cancerous microenvironment; and therefore, as a potential strategy in breast cancer therapy.