Marques Rute B, van Weerden Wytske M, Erkens-Schulze Sigrun, de Ridder Corrina M, Bangma Chris H, Trapman Jan, Jenster Guido
Department of Urology, Josephine Nefkens Institute, Erasmus Medical Center, P.O. Box 1738, 3000 DR, Rotterdam, The Netherlands.
Eur Urol. 2006 Feb;49(2):245-57. doi: 10.1016/j.eururo.2005.12.035. Epub 2006 Jan 6.
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.
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.
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.
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.
反映不同疾病阶段的前列腺癌(PC)模型系统对于研究PC的发生发展以及测试新的治疗方式至关重要。本综述总结了PC346进展模型的建立与特性,并将其与其他现有的人类PC细胞系和异种移植模型进行比较。
PC346模型源自原发性前列腺肿瘤的经尿道切除术。将肿瘤样本皮下植入无胸腺小鼠体内,从而产生一系列异种移植瘤,从中建立体外细胞培养。
PC346组包括具有从雄激素敏感到雄激素非依赖(AI)生长的激素反应特性的亚系。在雄激素缺乏条件下对雄激素敏感系进行体内和体外选择,重现了临床相关的复发现象,并导致雄激素受体(AR)途径发生一系列改变:AR突变、过表达和下调。
PC346组重现了临床PC不同阶段的许多生物学特征以及在激素难治性肿瘤中观察到的最常见的AR改变,是对有限的现有模型系统的宝贵补充。