Department of Urology, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Prostate. 2010 Apr 1;70(5):491-501. doi: 10.1002/pros.21083.
Prostate stem/progenitor cells function in glandular development and maintenance. They may be targets for tumor initiation, so characterization of these cells may have therapeutic implications. Cells from dissociated tissues that form spheres in vitro often represent stem/progenitor cells. A subset of human prostate cells that form prostaspheres were evaluated for self-renewal and tissue regeneration capability in the present study.
Prostaspheres were generated from 59 prostatectomy specimens. Lineage marker expression and TMPRSS-ERG status was determined via immunohistochemistry and fluorescence in situ hybridization (FISH). Subpopulations of prostate epithelial cells were isolated by cell sorting and interrogated for sphere-forming activity. Tissue regeneration potential was assessed by combining sphere-forming cells with rat urogenital sinus mesenchyme (rUGSM) subcutaneously in immunocompromised mice.
Prostate tissue specimens were heterogeneous, containing both benign and malignant (Gleason 3-5) glands. TMPRSS-ERG fusion was found in approximately 70% of cancers examined. Prostaspheres developed from single cells at a variable rate (0.5-4%) and could be serially passaged. A basal phenotype (CD44+CD49f+CK5+p63+CK8-AR-PSA-) was observed among sphere-forming cells. Subpopulations of prostate cells expressing tumor-associated calcium signal transducer 2 (Trop2), CD44, and CD49f preferentially formed spheres. In vivo implantation of sphere-forming cells and rUGSM regenerated tubular structures containing discreet basal and luminal layers. The TMPRSS-ERG fusion was absent in prostaspheres derived from fusion-positive tumor tissue, suggesting a survival/growth advantage of benign prostate epithelial cells.
Human prostate sphere-forming cells self-renew, have tissue regeneration capability, and represent a subpopulation of basal cells.
前列腺干/祖细胞在腺体发育和维持中发挥作用。它们可能是肿瘤起始的靶标，因此对这些细胞的特征描述可能具有治疗意义。在体外形成球体的分离组织中的细胞通常代表干/祖细胞。本研究评估了一组形成前列腺球体的人前列腺细胞的自我更新和组织再生能力。
从 59 份前列腺切除术标本中生成前列腺球体。通过免疫组织化学和荧光原位杂交（FISH）检测谱系标志物表达和 TMPRSS-ERG 状态。通过细胞分选分离前列腺上皮细胞的亚群，并检测其球体形成活性。通过将球体形成细胞与免疫缺陷小鼠的大鼠泌尿生殖窦间充质（rUGSM）皮下共培养来评估组织再生潜力。
前列腺组织标本具有异质性，包含良性和恶性（Gleason 3-5）腺体。在检查的大约 70%的癌症中发现了 TMPRSS-ERG 融合。前列腺球体从单个细胞以不同的速度（0.5-4%）发展而来，可以连续传代。在球体形成细胞中观察到基底表型（CD44+CD49f+CK5+p63+CK8-AR-PSA-）。表达肿瘤相关钙信号转导器 2（Trop2）、CD44 和 CD49f 的前列腺细胞亚群优先形成球体。球体形成细胞和 rUGSM 的体内植入再生了包含离散基底和腔层的管状结构。源自融合阳性肿瘤组织的前列腺球体中不存在 TMPRSS-ERG 融合，这表明良性前列腺上皮细胞具有生存/生长优势。
人前列腺球体形成细胞自我更新，具有组织再生能力，代表基底细胞的一个亚群。
