Číslo abstraktu: p20
Unfolding the mechanisms of cancer cell plasticity might contribute to future therapeutical approaches. Breast cancer stem cells (BCSC) are suggested to be the drivers of metastasis, resistance to chemotherapy and radiation. BCSC were previously shown to co-exist in diverse mesenchymal and epithelial states in different tumor sites. Mesenchymal state results from EMT (epithelial-to-mesenchymal transition) and epithelial from MET (mesenchymal-to-epithelial transition). To understand the relationship between EMT, MET and BCSC we used HER 2/neu-overexpressing primary mouse mammary carcinoma cell line (MMC) and its relapsed HER 2/neu antigen-negative variants (ANV). Analysis at the single cell level revealed different expression of surface stem cell markers (CD44, CD49f, CD133, Trop-2 and Sca-1), transcription factors responsible for stemness (Oct-3/4, Sox-2, Nanog) and EMT/MET regulators (Snail, Slug, Axl) amongst cell lines. We examined basal expression of epithelial and mesenchymal markers and also EMT regulators in various BCSC populations and expression after induced switch of phenotype via different signaling pathways. De-differentiation of ANV clones during the EMT transformation, accompanied by acquisition of Sca-1 expression, confers that the stemness and EMT might be related in mouse mammary carcinoma cells and their relapsed variants.
The authors would like to thank Dr. Keith L. Knutson for providing model cell lines. This work was supported by grants Histopark no. CZ.1.07/2.3.00/20.0185 and OrganoNET no. CZ.1.07/2.4.00/31.0245 of Ministry of Education, Youth and Sports, IGA MZD NT13573-4/2012, AV ČR M200041203, and by project FNUSA-ICRC (no. CZ.1.05/1.1.00/02.0123) from the European Regional Development Fund. Institutional support was provided by the Academy of Sciences of the Czech Republic.
- Suling L, et al. Breast Cancer Stem Cells Transition between Epithelial and Mesenchymal States Reflective of their Normal Counterparts. Stem Cell Reports, 2014.
- Knutson KL, et al. neu Antigen-Negative Variants Can Be Generated after neu-Specific Antipody Therapy in neu Transgenic Mice. Cancer Research, 2004.
Datum přednesení příspěvku: 24. 4. 2014