CRITICAL MOLECULAR MECHANISMS THAT MODIFY BONE MARROW-MESENCHYMAL STEM CELL BEHAVIOUR IN ADVANCED BREAST CANCER PATIENTS

BORZONE, FRANCISCO RAÚL; SANMARTIN, CECILIA; GIORELLO, MARÍA BELÉN; FERNÁNDEZ VALLONE, VALERIA BEATRIZ; MARTINEZ, LEANDRO MARCELO; PICCIONI, FLAVIA; BATAGELJ, EMILIO; FELDMAN, LEONARDO; PACIENZA, NATALIA; YANNARELLI, GUSTAVO; CHASSEING, NORMA ALEJANDRA

CABA

Congreso; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2020

Sociedad Argentina de Investigación Clínica

ductal, stage IIIB) develop osteolytic bone metastasis, due to theexistence of a pre-metastatic niche (PMN) that favours extravasation,migration, and proliferation of tumor cells. We found that bonemarrow (BM) mesenchymal stem cells (MSC) from BCP have lowercloning, proliferation, and osteogenic differentiation capacities thanhealthy donors (HD) MSC. A conserved pool of functional MSC isessential for preventing the PMN formation.Thus, our aim was to identify the molecular mechanisms responsiblefor the loss of function in MSC from BCP. For this purpose, westudied the expression of stemness markers (OCT4, SOX2, hTERT,CD49b, CD146, telomere length), triggers osteogenic differentiation(RUNX2 and BMP2) [qPCR], and the cellular oxidative state (ROSlevels) [FACS] in MSC from enriched cultures of BM aspirates fromBCP vs HD. We also evaluated the morphologic characteristics [Optical OpticalMicroscopy], proliferation capacity [Proliferation Assay], andcell cycle profile of MSC [FACS]. Besides, we compared the pool ofMSC in BM aspirates [RosetteSepTM].The results indicated that BCP-MSC (n=7) vs HD-MSC (n=7) had:lower expression levels of OCT4 (p=0.026), SOX2 (p=0.008),hTERT (p= 0.004), CD146 (p=0.041) and higher levels of CD49b(p=0.028), RUNX2 (P=0.039) and BMP2 (P=0.033); shortened telomerelength (p=0.002); increased ROS levels (p=0.036); decreasedproliferative capacity (p=0.03); higher relative proportions of cellsin G0/G1 phase (p=0.011) and lower in S phase (p=0.033); lowernumber of CFU-F (p=0.01); increased area (p=0.001), higher long(p=0.02) and short axis (p=0.001). In addition, BCP vs HD had apoor pool of BM MSC (p=0.006).In conclusion, the lower expression of OCT4 and SOX2 in MSC,would lead to an ineffective self-renewal, proliferation, and differentiationof these stem cells, providing insights about the molecularalterations in the BCP-MSC, key players in the development of thePMN.