The Function and Regulatory Mechanisms of Growth Differentiation Factor 15 and Caffeic Acid Phenethyl Ester in Tumorigenesis and Fibrosis of Human Bladder

The growth differentiation factor-15 (GDF15), a member of the TGF-β superfamily, affects the tumor biology and fibrosis of various organs; however, the biological functions of GDF15 in stroma and epithelial carcinoma in human bladder remain poorly understood. Caffeic acid phenethyl ester (CAPE), a bioactive component extracted from honeybee hive propolis, is considered as a new anti-cancer agent. Our preliminary data indicated that CAPE-inducing GDF15 downregulated not only the cell invasion of carcinoma cells but also the cell migration of stromal cells of the human bladder. Our preliminary data also suggested that CAPE induced phosphorylation of ERK, JNK, p38, or AMPK1/2 to modulate the gene expression of GDF15. The functions of GDF15 crosstalk between stromal-epithelial of the human bladder, up to date, is still not investigated yet. Therefore, in this three-year proposal, PI will focus on the understanding the functions of GDF15 in bladder fibrosis and bladder carcinoma cells and the determining the regulatory mechanisms of CAPE on GDF15 expression. The major goals are to (1) determine the potential biologic functions and regulatory mechanisms of GDF15 in human bladder cells in vitro and in vivo, (2) determine the signaling pathways of CAPE on GDF15 expression in human bladder stroma and carcinoma cells, (3) determine the anti-fibrosis activity of GDF15 in vitro. The proposal will be the first study not only to evaluate the crosstalk of GDF15 between fibrosis and tumorigenesis in stromal and epithelial cells of human bladder but to understand the GDF15 receptor in the human bladder cells. The novel data from this proposal will be excepted to employ these concepts in the early diagnosis and drug screen of the disease of bladder.

Project ID:PC10907-0949
External Project ID:MOST109-2320-B182-018-MY3