Fibroblast impact on expression of cancer stem cell genes in triple negative subtype of breast cancer in doxorubicin chemotherapy condition

Abstract

The role of fibroblasts in strengthening and creating the phenotype of cancer stem cells and on the other hand the effect of chemotherapy on the emergence of stem characteristics in breast cancer cells led us to investigate the effect of fibroblast stromal cells (as part of important and abundant tumor microenvironment in breast cancer) to discuss the expression of stem cell genes in the basal type of breast cancer after chemotherapy. Materials and Methods: This study was started in 2018 at the Immunology Research Center of Tabriz University of Medical Sciences and the research is of fundamental and basic type. All investigations were done in vitro and on MCF-7 and MDA-MB 231 cell lines as luminal and basal subgroups, respectively. The amount of change in the expression of OCT4, Nanog and KLF-4 genes, the amount of change in the expression of ALDH1 and morphological changes (epithelial to mesenchymal) in basal and luminal type breast cancer cells after culture with medium obtained from treated fibroblast cells was investigated with doxorubicin. Results: Both types of cells with paracrine secretions of normal fibroblasts have changed shape towards the epithelial and less aggressive state under the influence of chemotherapy. On the other hand, in both cell lines, the level of ALDH1 enzyme expression in the medium condition group was significantly lower compared to the control group, which indicates the reduction of stem cell characteristics through the reduction of ALDH1 enzyme expression due to the presence of paracrine secretions of fibroblast cells. Normal human cells are either basal subtype or luminal subtype next to cancer cells. The condition of fibroblast-derived medium under the conditions of chemotherapy with doxorubicin in luminal breast cancer cells only led to a decrease in KLF-4 gene expression and had no effect on the expression of Nanog and Oct-4 genes.