)- A CD105+ subpopulation of stromal cells from primary tumors of breast cancer patients promotes mesenchymal-like stem cell states.

OSINALDE TM; GIORELLO MB; BORZONE FR; CALVO JC.; PADIN MR.; WERNICKE A.; CHASSEING NA; VELLÓN L

Mar del Plata

Congreso; LXVIII Reunión anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2023

Sociedad Argentina de Investigación Clínica (SAIC)

Within the tumor microenvironment, certain subpopulations of stromal cells are able to trigger aberrant tissue reparative processes that include the acquisition/loss of cancer stem cell (CSC) states. We aimed to study whether conditioned media from CD105+ CD34- and CD105- CD34- subpopulations of spindle stromal cells (CD105+/CM and CD105-/CM, respectively) from primary tumor of breast cancer (BC, invasive ductal carcinoma, stage I-II) patients was able to affect CSC states in BC-derived MCF-7 and MDA-MB-231 cells. Previously, we observed that CD105+/CM increased more drastically mammosphere formation ability in MDA-MB-231 when compared to MCF-7 cells. Here, we tested CM from more patients, individually as well as pooled, and found that this trend was conserved, since CD105+/CM induced a 7,9-10,7 fold-time increase in mammosphere frequency in MDA-MB-231 cells, and a 2,2-3,15 fold-time increase in MCF-7 cells, whereas CD105-/CM did not generally induce significant changes in mammosphere formation in both cell lines when compared to control CM, as quantified by extreme limiting dilution assay (ELDA) and further statistical analysis with a specialized software (http://bioinf.wehi.edu.au/software/elda). Interestingly, when MCF-7 mammospheres generated in the presence or the absence of CD105+/CM and CD105-/CM were allowed to attach and spread onto gelatin under differentiating conditions (complete DMEM/F12 culture medium), we observed that mammospheres generated in CD105+/CM remained more frequently as such and spread less than those generated in control or CD105-/CM. These results support our previous findings that CD105+/CM promotes the generation of mesenchymal-like CSC states (MDA-MB-231) rather than epithelial-like CSC states (MCF-7), suggesting that CM from different subpopulations of stromal cells from the breast of BC patients not only differentially affect stem states, but may also affect differentiation and migration ability of BC-derived epithelial cells. Medicina (Bs. As.) 83 (supp V): abstract 389 (poster 132), pg 196, 2023.