The Early Cell Cultures from Prostate Cancer Tissue Produce Tissue Specific Epithelial and Cancer Markers

Prostate cancer (PCa) is a widespread oncogenic disease which in majority of patients proceeds in an indolent form. However, in some cases the indolent form is transformed into an aggres-sive metastatic incurable cancer. The most important task of PCa diagnostics is the search for early markers that allow predicting the transition of indolent cancer to an aggressive disease. There are now two effective preclinical models to study the PCa pathogenesis: patients derived xenografts (PDX) and patients derived organoids (PDO). Both models have limitations and are not affordable for wide research usage. In this work we investigated the ability of the prostate primary 2D cell cultures (PCC) from prostate cancer patients to produce epithelial and cancer markers. We found that early PCC are formed initially by epithelial cells which are progres-sively replaced with fibroblast-like cells. Early PCC contain tissue-specific stem cells that grow in 3D culture and form PDO similar to those from the prostate tissue. Early PCC and corre-sponding PDO from prostate cancer patients express the prostate basal, luminal epithelial and cancer markers AMACR, TMPRSS2-ERG and EZH2 which is a promising candidate to mark the transition from indolent to aggressive PCa. We have identified a diversity of TMPRSS2-ERG fu-sion transcripts in PCC and PDO, including new chimeric variants resulting from intra- and in-terchromosomal translocation. The results obtained suggest that early PCC from cancer and normal tissue sustain maternal prostate phenotype and may be used as a preclinical model to study the pathogenesis of PCa.