Development of a Microfluidic Model of a Human Prostate Gland for Cancer Research

Abstract

Prostate cancer is the second leading cause of cancer death in American men1. The prostate is a gland at the bladder base of males comprising a pseudo-stratified epithelium surrounded by a fibromuscular stroma2. Studies have shown that androgens regulate prostate development via signaling between the epithelium and the stroma2. We utilize a microfluidic-based system, prostate-on-a-chip (POC), developed for co-cultivation of human prostate epithelium and stroma to recapitulate the functions of a human prostate gland in vivo2 since it is difficult to establish a co-culture tissue in petri dishes. After successfully maintaining cultures of epithelial cells (iPECs) and stromal cells (BHPrSs) in fabricated microfluidic devices, epithelium differentiation was re-affirmed in epithelium/stroma co-cultures following 3 weeks incubation time. Some basal cells terminally differentiated into luminal cells, while acinus-like structures were formed in the epithelium, thereby confirming the PoC as a reliable in vitro model of the human prostate gland. Subsequently, the potential application of the PoC model for prostate cancer research was explored3. In cancerous epithelium/normal stroma (EMP/BHPrS) co-cultures, the cancerous epithelium was found to induce the initially normal stromal cells to assume a cancer-associated fibroblast (CAF) phenotype. In normal epithelium/cancerous stroma (iPEC/PIM1) co-cultures, Dox treatment of the PIM1 stroma induced the cells to over express biomarkers known to be associated with tumor progression. These results firmly establish the PoC not only as a superior model of the normal human prostate, especially in comparison with 2D cell cultures and animal models, but also as a promising platform to investigate biological mechanisms implicated in initiation, progression and proliferation of tumors in a human prostate cancer.