Cancer-Associated Fibroblasts Regulate the Plasticity of Breast Cancer Stemness through the Production of Leukemia Inhibitory Factor.
Nazanin VaziriLaleh ShariatiAli ZarrabiAli FarazmandShaghayegh Haghjooy JavanmardPublished in: Life (Basel, Switzerland) (2021)
Leukemia inhibitory factor (LIF), as a member of the interleukin-6 cytokine family, plays a complex role in solid tumors. However, the effect of LIF as a tumor microenvironment factor on plasticity control in breast cancer remains largely unknown. In this study, an in vitro investigation is conducted to determine the crosstalk between breast cancer cells and fibroblasts. Based on the results, cancer-associated fibroblasts are producers of LIF in the cocultivation system with breast cancer cells. Treatment with the CAF-CM and human LIF protein significantly promoted stemness through the dedifferentiation process and regaining of stem-cell-like properties. In addition, the results indicate that activation of LIFR signaling in breast cancer cells in the existence of CAF-secreted LIF can induce Nanog and Oct4 expression and increase breast cancer stem cell markers CD24-/CD44+. In contrast, suppression of the LIF receptor by human LIF receptor inhibition antibody decreased the cancer stem cell markers. We found that LIF was frequently overexpressed by CAFs and that LIF expression is necessary for dedifferentiation of breast cancer cell phenotype and regaining of cancer stem cell properties. Our results suggest that targeting LIF/LIFR signaling might be a potent therapeutic strategy for breast cancer and the prevention of tumor recurrence.
Keyphrases
- cancer stem cells
- breast cancer cells
- stem cells
- endothelial cells
- magnetic resonance
- acute myeloid leukemia
- epithelial mesenchymal transition
- binding protein
- bone marrow
- computed tomography
- signaling pathway
- magnetic resonance imaging
- young adults
- mesenchymal stem cells
- drug delivery
- optical coherence tomography
- anti inflammatory
- amino acid