The influence of tumor-associated macrophages on the HEXIM1 /SMAD/TGFβ axi̇s and the prostate cancer progression

Tumor-associated macrophages (TAMs) are a key component of the inflammatory microenvironment. TAMs can promote tumour progression, angiogenesis and metastases by secreting cytokines such as TGFβ, MMP9. HEXIM1 is a key regulator of prostate cancer development by virtue of being an inhibitor of the Cdk9 serine kinase activity. The expression levels of HEXIM1 will influence RNA Pol II-dependent transcription, Cdk9 regulation of the TGFβ /SMAD axis. In this study we analyzed the role of TAMs account, HEXIM1 expression and TGFβ /SMAD axis in the prostate cancer progression. One hundred patients who were diagnosed with PCa at Baskent University Hospital were selected. A diagnosis of PCa was reevaluated by histological examination of specimens obtained radical prostatectomy. TAMs were immunohistochemically labelled using CD68 monoclonal antibody. Immunohistochemistry for HEXIM1, TGFβ, SMAD2, SMAD7 and MMP9 was performed in each tissue. We observed increased TGFβ, SMAD2 ve HEXIM1 expression and decreased SMAD7 expression in prostate cancer tissue correlated with increased Gleason score, lymphovascular invasion, perineural invasion, extracapsular extension. Our results suggested that TAMs might be associated with increased HEXIM1, TGFβ, MMP9 expression and activity in prostate cancer. Based on these results, we propose that TAMs account and Hexim-1 protein significantly influences the TGFβ signaling. Thus, TAMs count, HEXIM1 and TGFβ signaling pathway is likely to play a significant role in prostate cancer progression.