High Aldehyde Dehydrogenase Activity Identifies Tumor-Initiating and Metastasis-Initiating Cells in Human Prostate Cancer

Abstract

Metastatic progression of advanced prostate cancer is a major clinical problem. Identifying the cell(s) of origin in prostate cancer and its distant metastases may permit the development of more effective treatment and preventive therapies. In this study, aldehyde dehydrogenase (ALDH) activity was used as a basis to isolate and compare subpopulations of primary human prostate cancer cells and cell lines. ALDH-high prostate cancer cells displayed strongly elevated clonogenicity and migratory behavior in vitro. More strikingly, ALDH-high cells readily formed distant metastases with strongly enhanced tumor progression at both orthotopic and metastatic sites in preclinical models. Several ALDH isoforms were expressed in human prostate cancer cells and clinical specimens of primary prostate tumors with matched bone metastases. Our findings suggest that ALDH-based viable cell sorting can be used to identify and characterize tumor-initiating and, more importantly perhaps, metastasis-initiating cells in human prostate cancer. Cancer Res; 70(12); 5163-73. ©2010 AACR.

Understanding cancer stem cell heterogeneity and plasticity

“…Similarly, stem-like cancer cells have been reported in human cancers of the prostate [87][88][89][90][91][92][93][94][95][96][97][98][99][100], lung [101][102][103][104][105][106][107][108][109][110][111], and many other organs (liver, pancreas, kidney, bladder, ovary, etc). In prostate cancer, tumor-initiating cells have been identified in xenografts in CD44 + [90,96], CD44 + α2β1 + [91], TRA-1-60 + CD151 + CD166 + [99], and ALDH + [97,98] populations as well as in SP [87] and holoclones [94].…”

“…In prostate cancer, tumor-initiating cells have been identified in xenografts in CD44 + [90,96], CD44 + α2β1 + [91], TRA-1-60 + CD151 + CD166 + [99], and ALDH + [97,98] populations as well as in SP [87] and holoclones [94]. The interrelationship between these tumorigenic subsets remains currently unclear except that the CD44 + α2β1 + phenotype greatly enriches tumorinitiating cells compared to CD44 + phenotype alone [91].…”

Mechanism of the Mesenchymal–Epithelial Transition and Its Relationship with Metastatic Tumor Formation

“…Mounting evidence indicates that CSCs are also involved in colonization and metastases formation (115)(116)(117). In addition to contributing to the generation of CSCs, EMT may give differentiated tumor cells the ability to self-renew, thus allowing the successful establishment of secondary tumors composed of cancer cells with heterogeneity at distant sites (103,118,119).…”

Sphingosine-1-phosphate promotes expansion of cancer stem cells via S1PR3 by a ligand-independent Notch activation

“…G rowing evidence suggests that many types of cancer, including breast, lung and prostate cancer, are initiated from a small population of cancer stem cells (CSCs; also called tumour-initiating cells) [1][2][3][4][5][6][7][8] . This minor population produces the bulk of cancers through continuous self-renewal and differentiation, which contributes to cancer heterogeneity.…”