Investigation of inflammation related epithelial-mesenchymal transition mechanism in metastatic prostate cancer progression
Project no. 23063 · Status: Kapanmış (Yayın bekleniyor) · 2021
Summary
<p>In this project, the molecular effect of the tumor suppressor NKX3.1 protein, which is critical for prostate cells, on the EMT mechanism in prostate cancer cell lines under inflammatory microenvironmental conditions was examined. In our studies, cell culture models representing the in vitro inflammatory microenvironment were designed with LNCaP, cells. To represent inflammation-related NKX3.1 protein loss and the induction of EMT in the inflammatory environment in cell culture, TNF-α/TGF-β1 cytokine induction were performed, and NKX3.1 expression was introduced into the cells to determine whether the levels of EMT proteins and cell localizations differ depending on the presence of NKX3.1. Its effect on the anoikis resistance of cells and epithelial-stromal interactions was investigated. Expressional change of EMT-related proteins due to NKX3.1 expression and inflammation in LNCaP cells was examined. NKX3.1 is a developmentally critical gene that is required for normal prostate survival and functions in stem cell embryogenesis. The EMT phenotype and the cancer stem cell phenotype have identical characteristics. In prostate cancer cells having ectopic NKX3.1, there is a correlation between increased NKX3.1 and increased EMT-related proteins. </p><p>In conclusion, NKX3.1 suppresses cell viability and anoikis resistance due to its tumor suppressor role in normal conditions and low-dose inflammatory conditions however, supports mesenchyme-like cell morphology in higher-dose, long-term inflammatory conditions and has a supportive role in increasing level of EMT proteins. In co-culture studies, it was determined that co-cultured WPMY1 cells (prostate myofibroblast cells) contributed to the increased EMT-related protein expressions induced by inflammatory microenvironment in LNCaPs (epithelial metastatic prostate cancer cells). Results contribute to identification of novel EMT-related therapeutic targets in inflammation-induced prostate cancer progression.</p>