Bone marrow-derived mesenchymal stromal cells induce the release of free circulating microRNAs by triple negative breast cancer cells.

PICCIONI FV.; FARRÉ PL ; BORZONE FR; MASSILLO CL; DALTON GN; RODRÍGUEZ ARCAPALO SV; ROTH FA; SCHARGORODSKY M; CHASSEING NA; DE SIERVI A

Mar del Plata

Congreso; Reunión Conjunta de la Sociedad Argentina de Investigación Clínica (SAIC), la Sociedad Argentina de Inmunología (SAI) y la Sociedad Argentina de Fisiología (SAFIS) 2018.; 2018

SAIC, SAI y SAFIS

Medicina (Bs.As.) 2018, vol 78 sup 3: abst 458, pg 112. Abstract: The main cause of death in patients with breast cancer (BC) is due to the metastasis ofthe primary tumor. Particularly, 60-70% of patients with advanced BC develop bone metastases. It has been reported that mesenchymal stromal cells (MSCs), that include mesenchymal stem cells, precursor and progenitor cells, stimulate breast cancer cellsto induce proliferation, invasion and migration to other niches, through several factors.MicroRNAs (miRNAs) are key regulators of tumorigenesis and tumor progression, andit is now known that they can circulate in the peripheral blood, which makes them promising biomarkers. Previous results from our group established a list of miRNAs obtained from breast allografts generated by 4T1 triple-negative cells in mice, which are differentially expressed in advanced stage vs. early stage. In addition, they were also found in the plasma of these mice. In this work, our aim was to identify the miRNAs released by MSCs and 4T1 tumor cell interaction. We generated a conditioned medium (MCo) from a primary culture of bone marrow MSCs (MCo-MSCs) from mice.Then, 4T1 cells were treated or not with MCo-MSCs. After 24 h, 4T1 cells were washedand incubated with culture medium (MCo-MSCs 4T1) for 48 h. Total RNA was isolated from these MCo. MiRNAs released were detected using stem-loop RT-qPCR. Results showed that the treatment with MSCs-MCo increased the release of miR-125b-5p,miR-221-3p and miR-21-5p by 4T1 cells, specially these last two. Furthermore, miRNAs221-3p and -21-5p were released by MSCs. We can conclude that MSCs induce the release of miRNAs by 4T1 cells, mainly miR-21 and miR-221, which are known to be involved in the processes of mesenchymal-epithelial transition, proliferation and migration of breast tumor cells, as well as in the activity of tumor-associated fibroblasts.