Interleukins 4 and 6 in Prostate Cancer progression

Prostate cancer (PCa) is one of the most common male cancers. Androgen deprivation is still a key therapeutic strategy in PCa. However, a small number of prostate cancer cells manage to survive anti-androgen therapies and is on the basis of relapses to a castration resistance PCa (CRPCa) state within one to two years. Several groups have been suggested that current therapies kill proliferating differentiated cells, but undifferentiated quiescent cancer stem cells (CSCs) survive and are responsible for relapse. Beside the development of CRPC it has shown that androgen ablation induces T cell infiltration of the prostate gland, leading to T cellmediated inflammation. Inflammation processes are regulated by cytokines which play an important role in the crosstalk between cancer cells and the microenvironment. Several cytokines e.g. interleukin (IL)-6 and IL-4 have been identified as an important factor in PCa progression. High IL-6 protein levels correlate with advanced stages and poor prognosis of PCa. In vitro studies demonstrated that IL- 6 treatment increase androgen receptor activity what lead to an increased tumor cell proliferation or differentiation. Also it has been shown that IL-6 increases PCa cells resistance to the anti-androgen bicalutamide. Furthermore, data from a phase I study of an anti-interleukin-6 therapy showed a downregulation of genes implicated in tumorigenesis. Although the role of IL4 has been less investigated in PCa, it is known to be elevated in tissue of PCa. Recently, it has been reported that IL-4 activates the androgen receptor in a ligandindependent manner by increasing the expression of co-activators CBP/p300. Interestingly, a morphologic change of the PC3 cell line to a more dedifferentiated phenotype was observable after longterm IL-4 treatment. Although changes in proliferation after treatment with IL-4 were not observed, clonogenic assays with primary PCa cells revealed that IL-4 increases the number of colonies. Furthermore, it has been shown that CSCs have an increased level of IL-4 receptor mRNA compared with the more differentiated cells. Concluded, it has been shown that cytokines play an important role in Prostate Cancer tumor initiation, progression and the development of therapy resistance. Because of this they are an ideal target for the development of new therapy strategies. Amniotic fluid stem cells and their clinical implication Kapil Dev, Mokrý Jaroslav, Diaz Daniel, Rishikysh V. Pisal Department of Histology and Embryology, Charles University in Prague, Medical Faculty in Hradec Kralove, Czech Republic Human amniotic fluid has been used in prenatal diagnosis for more than 70 years and existence of stem cells in amniotic fluid was reported for the first time almost eight years ago. It has proven to be a safe, reliable and simple screening tool for a wide variety of developmental and genetic diseases. Today, amniotic fluid stem (AFS) cells are widely accepted as a new powerful tool for basic research as well as for the establishment of new stem cell based therapy concepts. Human AFS cells have become an attractive stem cell source for medical therapy due to both their ability to propagate as stem cells and the lack of ethical debate that comes with the use of embryonic stem cells. AFS cells are known to yield a number of cell types which are multipotent, ethically derived, genetically stable, easily grown, expanded and possess favorable immunogenicity, which has resulted in an increasing interest for use in various diseases. Different forty six samples of AFS cells were carried away for culturing and characterization purposes with RT-PCR, immunocytochemistry and staining methods. Ten samples were used for chemical induced guided differentiation of amniotic fluid derived cells into neurogenic, adipogenic and osteogenic cells followed by particular staining i.e. oil-red-O and von Kossa for morphological bases and RTPCR confirmation with nestin, fatty acid binding protein (FAB P)-4 and osteocalcin, respectively. These cells are characterized by the expression of mesenchymal as well as pluripotency markers (CD29, CD44, CD73, CD90, CD105, CD133, Oct-4 and SSEA -4) and neural (nestin, βIII-tubulin, NEFH) markers. They are capable of differentiating into diverse derivatives in vitro. Clonal human lines verified by retroviral marking were induced to differentiate into into various cell lineages, including hematopoietic, adipogenic, osteogenic, myogenic, endothelial, hepatogenic, chondrocytic, pulmonary, cardiac and neurogenic. These undifferentiated cells proliferated without feeders layer and conserve a normal karyotype with long telomeres over long culture periods. Most important their own advantageous properties, amniotic fluid stem cells are emerging as a novel source in anticancer and antitumor therapy. This work was supported by the European Social Fund and the state budget of the Czech Republic, project no. CZ.1.07/2.3.00/30.0022.