Department of Urology, University of Michigan Medical School, 5111 CCGC, 1500 E. Medical Center Dr., Ann Arbor, MI 48109-0940, USA.
In Vivo. 2011 Jan-Feb;25(1):69-76.
Cancer stem cells (CSCs) have been shown to be a small stem cell-like cell population which appears to drive tumorigenesis, tumor recurrence and metastasis. Thus, identification and characterization of CSCs may be critical to defining effective anticancer therapies. In prostate cancer (PCa), the CD44(+) cell population appears to have stem cell-like properties including being tumorigenic. The enzyme aldehyde dehydrogenase (ALDH) has been found to identify hematopoietic stem cells and our aim was to determine the utility of ALDH activity and CD44 in identifying PCa stem cell-like cells in PCa cell lines.
LNCaP cells and PC-3 cells were sorted based on their expression of CD44 and ALDH activity. The cell populations were investigated using colony-forming assays, invasion assays, sphere formation experiments in a non-adherent environment and 3-D Matrigel matrix culture to observe the in vitro stem-cell like properties. Different sorted cell populations were injected subcutaneously into NOD/SCID mice to determine the corresponding tumorigenic capacities.
ALDH(hi) CD44(+) cells exhibit a higher proliferative, clonogenic and metastatic capacity in vitro and demonstrate higher tumorigenicity capacity in vivo than did ALDH(lo) CD44(-) cells. The tumors recapitulated the population of the original cell line. However, ALDHlo CD44(-) cells were able to develop tumors, albeit with longer latency periods.
ALDH activity and CD44 do not appear to identify PCa stem cells; however, they do indicate increased tumorigenic and metastatic potential, indicating their potential importance for further exploration.
癌症干细胞（CSCs）已被证明是一小群具有干细胞样特性的细胞，似乎可以驱动肿瘤发生、肿瘤复发和转移。因此，鉴定和表征 CSCs 对于确定有效的抗癌治疗方法可能至关重要。在前列腺癌（PCa）中，CD44(+)细胞群似乎具有干细胞样特性，包括致瘤性。醛脱氢酶（ALDH）已被发现可鉴定造血干细胞，我们的目的是确定 ALDH 活性和 CD44 在鉴定 PCa 细胞系中的 PCa 干细胞样细胞中的效用。
根据 LNCaP 细胞和 PC-3 细胞表达 CD44 和 ALDH 活性对其进行分选。使用集落形成测定、侵袭测定、无粘附环境中的球体形成实验以及 3-D Matrigel 基质培养来研究细胞群体，以观察体外干细胞样特性。将不同分选的细胞群皮下注射到 NOD/SCID 小鼠中，以确定相应的致瘤能力。
ALDH(hi) CD44(+)细胞在体外具有更高的增殖、克隆形成和转移能力，并且在体内表现出更高的致瘤能力，比 ALDH(lo) CD44(-)细胞高。肿瘤再现了原始细胞系的群体。然而，ALDHlo CD44(-)细胞能够形成肿瘤，尽管潜伏期较长。
ALDH 活性和 CD44 似乎不能鉴定 PCa 干细胞；然而，它们确实表明了更高的致瘤和转移潜力，表明它们对进一步探索具有潜在重要性。
