The human PC346 xenograft and cell line panel: A model system for prostate cancer progression

Objective: Prostate cancer (PC) model systems that reflect the different disease stages are essential for studying the development and progression of PC and for testing new treatment modalities. This review summarizes the establishment and characterization of the PC346 progression model and compares it to other available human PC cell lines and xenografts. Methods: The PC346 model was derived from the transurethral resection of a primary prostate tumor. Tumor samples were subcutaneously implanted into athymic mice, which resulted in the development of a series of xenografts from which in vitro cell cultures were established. Results: The PC346 panel includes sublines with hormone-response characteristics that range from androgen-sensitive to androgen-independent (AI) growth. In vivo and in vitro selection of androgen-sensitive lines under androgen-depleted conditions replicated the clinically relevant relapse phenomenon, and resulted in a series of modifications in the androgen-receptor (AR) pathway: AR mutation, overexpression, and downregulation. Conclusions: The PC346 panel reproduces many biological characteristics of the different phases of clinical PC and the most common AR modifications observed in hormone-refractory tumors, being a valuable addition to the limited collection of available model systems. (c) 2005 Elsevier B.V. All rights reserved.