MIGRATION CAPACITY OF BONE MARROW-MESENCHYMAL STEM CELLS FROM PATIENTS WITH ADVANCED BREAST CANCER: A NOVEL APPROACH OF BONE PRE-METASTATIC NICHE

BORZONE, FRANCISCO RAÚL; GIORELLO, MARÍA BELÉN; MUNICOY, JULIETA; PICCIONI, FLAVIA; LABOVSKY, VIVIAN; FERNÁNDEZ VALLONE, VALERIA BEATRIZ; BATAGELJ, EMILIO; FELDMAN, LEONARDO; YANNARELLI, GUSTAVO; MARTINEZ, LEANDRO MARCELO; CHASSEING, NORMA ALEJANDRA

Buenos Aires City

Congreso; LXII Reunión Anual de Sociedades de Biociencias (SAIC); 2017

Sociedad Argentina de Investigación Clínica

Recent reports indicated that self-renewal, proliferation, as well as migration capacity of bone marrow (BM) mesenchymal stem cells (MSC) areessential properties for bone regeneration processes.We found that MSC from untreated advanced breast cancer patients (BCP,invasive ductal, stage III-B) have lower cloning, proliferation and osteogenic differentiation capacities than healthy donors (HD)-MSC. Also, BCP-MSCfavouredosteoclastogenesis from BM hematopoietic precursors. Here, we aimed to evaluate migratory capacity of MSCfrom BM of advanced BCP and different parameters that regulate it, which isindispensable for the processes of osteogenesis and bone vascularization.For this purpose, we studied the % of MSC that express CD146 and the level of expression/MSC (Flow Cytometry=FC), as well as TERT activity (RT-PCR), telomere length(RT-PCR), and intracytoplasmatic/ mitochondrial ROS production (FC) in MSC of BCP and HD.Also, we analyzed the expression of total and phosphorylated (P) β-catenin in these stem cells (Western-blot and immunocytochemistry) and the production of pro-MMP-2, active-MMP-2, SDF-1 and CCL-2 levels (ELISA) in conditioned media of fibroblast colony forming units (1CFU-F = 1MSC). Finally, we studiedtheir migration capacity (Transwell assay).The results indicated that BCP-MSC vs HD-MSC had: lower % of MSC-CD146(+) [p=0.0446]; decreased CD146 relative fluorescence index (p=0.0023);decreased TERT activity (p=0.0416);increased P-β-cateninexpression(p=0.0001); increasedP-β-catenin/ total β-catenin ratio (p=0.0410); increased total ROS levels (p=0.0286); decreased SDF-1, pro and active MMP-2 levels (p=0.0334, 0.0010, 0.0030); increased CCL-2 level (p=0.0370)and poor migration capacity (p=0.0376).Findings suggest that alteration of MSC migration provide more insight to better defining the development of the BM and bone ?pre-metastatic niche?.Also, data show some possible targets aimed to restore migratory capacity of BCP-MSC.