Endocrine Abstracts

Carcinoma-associated fibroblasts (CAFs) within the stromal tumor microenvironment play a key role in promoting the development, progression and therapy resistance of prostate cancer (PCa). However, the stromal compartment is not targeted by current treatment strategies. Elevated secretion of transforming growth factor beta (TGFβ) by epithelial cells in prostate intraepithelial neoplasia (PIN) lesions and tumor cells induces fibroblast activation to the CAF phenotype and i...

Mitochondria play a vital role in cellular bioenergetics, providing energy via oxidative phosphorylation (OXPHOS) and metabolic intermediates. Aerobic ATP production is orchestrated by a multi-enzyme complex, which uses the electrons gained during oxidation of energy substrates to generate an electrochemical potential across the mitochondrial (mt) membrane that drives ATP synthase. Although there is evidence that mitochondrial function as well as mtDNA mutations might play a r...

Metabolic reprogramming resulting in significant alterations of the energy metabolism is a hallmark of prostate cancer (PCa). In this study we performed a comprehensive metabolic analysis of various human (LNCaP, DuCaP, PC-3, Du145) and murine PCa cell lines differing in the expression of the tumor suppressor phosphatase and tensin homolog (PTEN). In line with previous studies we found that PTEN- PCa cells (LNCaP, PC-3) had a higher glycolytic activity than PTEN<sup...

A diet rich in phytoestrogens such as flavonoids has been attributed as one of the reasons for the low incidence of prostate cancer in Asia as opposed to Western countries with a diet rich in fat and meat and the highest incidences of this cancer. In many cellular models of prostate cancer these substances, the prototype of which is genistein, inhibit cell proliferation and cell cycle progression and enhance the rate of apoptosis. The molecular mechanisms involve modulation of...

The use of more tissue-mimetic 3-dimensional (3D) cell culture models for in vitro drug screening has significantly increased in the past with the expectation to overcome with over-interpretation of drug effects obtained with conventional 2D cultures. In this study, we characterized 3D prostate cancer (PCa) organoids where PCa epithelial cells (LNCaP, DuCaP, LAPC4) were cultured alone or with PCa-associated fibroblasts (CAFs) in 96 well hanging drop plates in order to...

Enzalutamide is an androgen receptor (AR) inhibitor approved for therapy of metastatic castration resistant prostate cancer. However, clinical application revealed that 30 to 40% of patients acquire resistance after a short period of treatment. Currently, the molecular mechanisms underlying such insensitivities are not completely understood, partly due to a lack of model systems. In the present study we established three different cellular models of enzalutamide resistance inc...