Role of Fetuin-A in Prostate Cancer Initiation, Progression and Prognosis
Josiah Ochieng, PhD
Robert J. Matusik, PhD
Zhenbang Chen, PhD
Even though the growth of prostate cancer (PCa) is largely driven by androgens, a subset usually develops that is refractory to androgen ablation (also known as castration resistant PCa; CRPC) with potential for metastasis. Preliminary data from our laboratory has implicated fetuin-A, also known as alpha 2-Heremans-Schmid glycoprotein (AHSG), in the growth of PCa cells and in the production of “uptake-competent” exosomes. The objective of the proposed studies is to define the role and significance of fetuin-A in prostate cancer progression. We hypothesize that PCa cells express ectopic fetuin-A which is secreted and taken up by the cells via TLR4 to mediate the biogenesis of ‘uptake-competent’ exosomes that promote PCa growth via activation of pAKT/pERK; moreover, we postulate that elevated fetuin-A expression serves as a prognostic biomarker for PCa.
1) To determine if fetuin-A expression is higher in AA PCa tissues relative to Caucasian American (CA) PCa tissues and whether high fetuin-A expression is associated with high Gleason Scores (>6) and enhanced pAKT and pERK.
2) To determine the role of ectopic fetuin-A in exosome biogenesis, promotion of 2-D and 3-D growth, motility and invasive capacity of PCa cells.
3) To investigate the efficacy of targeting fetuin-A mediated signaling on the suppression of prostate tumor initiation and growth in mice.