Low Oct4 expression in mesenchymal stem cells contributes to the development of the bone marrow pre-metastatic niche in advanced breast cancer patients

BORZONE F.; FELDMAN L.; CHASSEING NA.; MALVICINI R.; BATAGELJ E.; YANNARELLI G.; SANMARTIN C.; MARTINEZ L.; PACIENZA N.

Buenos Aires

Congreso; Buenos Aires Breast Cancer Symposium 2021; 2021

Theimbalance between osteogenesis and osteoclastogenesis in the bonemarrow (BM) microenvironment seems to play an essential role in theestablishment of bone metastasis in untreated advanced breast cancerpatients (BCP). We have previously found that this lack of balance isproduced, among other factors, by a lower self-renewal,proliferation, and osteogenic differentiation capacity ofBM-mesenchymal stem cells (MSCs). Mechanisms mediating thesecharacteristic changes remain elusive. Here, we evaluated theexpression of the osteoprogenitor marker CD146 (Flow cytometry),telomerase activity (qPCR), telomere length (qPCR), as well as theexpression of the pluripotency factors Oct4 and Sox2 (qPCR) inBM-MSCs from clinical stage IIIb BCP (n=8) vs. healthy volunteers(HV; n=8). We found that MSCs from BCP had lower percentage of CD146+cells (p=0.04), decreased CD146 relative fluorescence index(p=0.002), lower telomerase activity (p=0.04), and shortened telomerelength (p=0.002) compared with HV. Moreover, Oct4 and Sox2 expressiondecreased by 54% (p=0.03) and 72% (p=0.009) in BCP-MSCs,respectively. Interestingly,Oct4 silencing impaired the ability of BM-MSCs to differentiate intoosteoblasts (p