Uzgare Aarti R, Xu Yi, Isaacs John T
Division of Experimental Therapeutics, Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland 21231, USA.
J Cell Biochem. 2004 Jan 1;91(1):196-205. doi: 10.1002/jcb.10764.
The prostatic epithelium is functionally organized in stem cell units. This unit consists of a slow turn over stem cell within the basal epithelial layer which can replenish itself and provide progeny which differentiate down either a neuroendocrine or exocrine pathway. The maturation along the exocrine pathway initially involves transit amplifying cells within the basal layer proliferating and subsequently the progeny maturing into intermediate cells. These intermediate cells migrate into the luminal layer where they terminally differentiate into non-proliferative secretory luminal cells which express prostate specific differentiation markers, like PSA. A growing body of experimental evidence has identified the proliferating transit amplifying/intermediate cells as the cells of origin for the common prostatic adenocarcinomas. Using a series of growth characteristics, and mRNA and protein markers, we have validated that primary cultures can be established in serum free defined media from surgically resected human prostates which are composed of essentially pure population of transit amplifying cells. At each serial passage, the subsequent cultures undergo enhanced maturation into intermediate cells and by the 7-10th passage these cells eventually lose their proliferative ability. This study validates that these cells are a useful and relevant system for the determination of molecular events involved in prostatic carcinogenesis.
前列腺上皮在干细胞单位中呈功能性组织。该单位由基底上皮层内的一个更新缓慢的干细胞组成，它能够自我补充并产生后代，这些后代可沿着神经内分泌或外分泌途径分化。沿着外分泌途径的成熟最初涉及基底层内的过渡增殖细胞增殖，随后其后代成熟为中间细胞。这些中间细胞迁移到管腔层，在那里它们最终分化为表达前列腺特异性分化标志物（如PSA）的非增殖性分泌管腔细胞。越来越多的实验证据已将增殖的过渡增殖/中间细胞确定为常见前列腺腺癌的起源细胞。利用一系列生长特性以及mRNA和蛋白质标志物，我们已经证实，可以在无血清限定培养基中从手术切除的人类前列腺建立原代培养物，这些培养物基本上由纯的过渡增殖细胞群体组成。在每次传代时，后续培养物会增强成熟为中间细胞，到第7至10代时，这些细胞最终失去增殖能力。这项研究证实，这些细胞是用于确定前列腺癌发生过程中分子事件的有用且相关的系统。
