BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.
BACKGROUND: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. MATERIALS AND METHODS: 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/SCIDmice to determine the corresponding tumorigenic capacities. RESULTS: 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. CONCLUSION: 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.
Authors: M Margarida Bernardo; Alexander Kaplun; Sijana H Dzinic; Xiaohua Li; Jonathan Irish; Adelina Mujagic; Benjamin Jakupovic; Jessica B Back; Eric Van Buren; Xiang Han; Ivory Dean; Yong Q Chen; Elisabeth Heath; Wael Sakr; Shijie Sheng Journal: Cancer Res Date: 2015-07-24 Impact factor: 12.701