Investigation on markers of inflammation-induced epithelial-mesenchymal transition and cancer stem cell in metastatic prostate cancer

Project no. 23389 · Status: Kapanmış (Yayın bekleniyor) · 2022

Summary

Inflammation-induced cancer progression plays an important role in the transition to the metastatic castration-resistant prostate cancer stage. In the inflammatory tumor microenvironment, increased cytokine concentrations also contribute to the transition to the metastatic stage by initiating epithelial-mesenchymal transition (EMT). NKX3.1 is a prostate-specific transcription factor, and its loss leads to the development of prostate cancer. In addition, it has been shown that in cases of metastatic castration-resistant prostate cancer, there are cells expressing NKX3.1 and these cells have progenitor properties. Therefore, it is thought that NKX3.1 may be effective in the EMT and stem cell phenotype in metastatic prostate cancer cells and therefore in the development of metastatic prostate cancer.In this project, considering that EMT and cancer stem cells have a similar phenotype, the aim is to identify the factors that play a role in EMT and cancer stem cell formation in the development of metastatic prostate cancer, depending on the inflammatory microenvironment and NKX3.1 expression. The importance of loss of NKX3.1 expression and its recovery in the castration-resistant stage for EMT and prostate cancer stem cell phenotype triggered by the inflammatory tumor microenvironment and possible altered prostate cancer stem cell markers have been identified. For this, the in vitro inflammatory microenvironment model was used to represent inflammation-associated NKX3.1 protein loss and induction of EMT in the inflammatory environment in cell culture. Molecular markers effective in EMT triggered in this way and NKX3.1 expression and changes were investigated in metastatic prostate cancer cell lines LNCaP, Du145 and PC3 cells using immunoblotting, immunofluorescence, PCR array, and RNA sequencing, which is a more holistic approach. It was evaluated that the data obtained contributed to the identification of factors playing a role in inflammation-related EMT and cancer stem cell in the development of metastatic prostate cancer and to the identification of novel therapeutic targets.

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