INVESTIGADORES
DE SIERVI Adriana
congresos y reuniones científicas
Título:
Bone marrow-derived mesenchymal stromal cells induce the release of free circulating microRNAs by triple negative breast cancer cells.
Autor/es:
PICCIONI F; FARRÉ PL; BORZONE F; RODRIGUEZ S; ROTH F; SCHARGOROSKY M; DALTON GN; MASSILLO C; CHASSEING NA; DE SIERVI A
Lugar:
Mar del Plata
Reunión:
Congreso; LXIII Reunión Annual de la Sociedad Argentina de Investigación Clínica; 2018
Resumen:
The main cause of death in patients with breast cancer (BC) is dueto the metastasis of the primary tumor. Particularly, 60-70% of patientswith advanced BC develop bone metastases. It has been reportedthat mesenchymal stromal cells (MSCs), that include mesenchymalstem cells, precursor and progenitor cells, stimulate breastcancer cells to induce proliferation, invasion and migration to otherniches, through several factors. MicroRNAs (miRNAs) are key regulatorsof tumorigenesis and tumor progression, and it is now knownthat they can circulate in the peripheral blood, which makes thempromising biomarkers. Previous results from our group establisheda list of miRNAs obtained from breast allografts generated by 4T1triple-negative cells in mice, which are differentially expressed inadvanced stage vs. early stage. In addition, they were also foundin the plasma of these mice. In this work, our aim was to identifythe miRNAs released by MSCs and 4T1 tumor cells interaction. Wegenerated a conditioned medium (MCo) from a primary culture ofbone marrow MSCs (MCo-MSCs) from mice. Then, 4T1 cells wereexposed or not to MCo-MSCs. After 24 h, 4T1 cells were washedand incubated with culture medium for 48 h (MCo-MSCs 4T1). TotalRNA was isolated from these MCo. MiRNAs released to the mediumwere detected using stem-loop RT-qPCR. Results showed thatMCo-MSCs exposure increased the release of miR-125b-5p, miR-221-3p and miR-21-5p by 4T1 cells. Furthermore, miR-221-3p andmiR-21-5p were released by MSCs. We conclude that MSCs inducethe release of miRNAs by 4T1 cells, mainly miR-21-5p and miR-221-3p, which are known to be involved in the processes of mesenchymal-epithelial transition, proliferation and migration of breast tumorcells, as well as in the activity of tumor-associated fibroblasts.