title: ALDH activity indicates increased tumorigenic cells, but not cancer stem cells, in prostate cancer cell lines.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.affiliation: Department of Urology, University of Michigan Medical School, 5111 CCGC, 1500 E. Medical Center Dr., Ann Arbor, MI 48109-0940, USA.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Yu
authors.forename: Zhi
authors.initials: Z
authors.lastname: Yao
authors.forename: Jinlu
authors.initials: J
authors.lastname: Dai
authors.forename: Honglai
authors.initials: H
authors.lastname: Zhang
authors.forename: June
authors.initials: J
authors.lastname: Escara-Wilke
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Zhang
authors.forename: Evan T
authors.initials: ET
authors.lastname: Keller
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000032:analysis*; D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis*; D045744:Cell Line, Tumor; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D018960:Hyaluronan Receptors / Q000032:analysis; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D014411:Neoplastic Stem Cells / Q000201:enzymology* / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; C497483:CD44 protein, human; D018960:Hyaluronan Receptors; D000444:Aldehyde Dehydrogenase