ALDH1-bright epithelial ovarian cancer cells are associated with CD44 expression, drug resistance, and poor clinical outcome.
The role of aldehyde dehydrogenase 1 (ALDH1) as an ovarian cancer stem cell marker and its clinical significance have rarely been explored. We used an Aldefluor assay to isolate ALDH1-bright (ALDH1(br)) cells from epithelial ovarian cancer cell lines and characterized the properties of the stem cells. ALDH1(br) cells were enriched in ES-2 (1.3%), TOV-21G (1.0%), and CP70 (1.2%) cells. Both ALDH1(br) and ALDH1(low) cells repopulated stem cell heterogeneity, formed spheroids, and grew into tumors in immunocompromised mice, although these processes were more efficient in ALDH1(br) cells. In the ES-2 and CP70 cells, ALDH1(br) cells conferred more chemoresistance, and were more enriched in CD44 (by 1.74-fold and 5.18-fold, respectively) than in CD133 (by 1.39-fold and 1.17-fold, respectively), compared with ALDH1(low) cells. Immunohistochemical staining for ALDH1 on a tissue microarray containing 84 epithelial ovarian cancer samples revealed that patients with higher ALDH1 expression (>50%) had poor overall survival, compared with those with lower ALDH1 (P = 0.004) and yielded an odds ratio of death of 2.43 (95% CI = 1.12 to 5.28) by multivariate analysis. The results did not support ALDH1 alone as an ovarian cancer stem cell marker, but demonstrated that ALDH1 is associated with CD44 expression, chemoresistance, and poor clinical outcome. The use of a combination of ALDH1 with other stem cell markers may help define ovarian cancer stem cells more stringently.
Laboratory of Epigenetics and Cancer Stem Cells, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, China; Graduate Institute of Medical Sciences, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, China; Department of Obstetrics and Gynecology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, China.
Yu-Chi
YC
Wang
Laboratory of Epigenetics and Cancer Stem Cells, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, China.
Yi-Te
YT
Yo
Laboratory of Epigenetics and Cancer Stem Cells, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, China; Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, China.
Hsin-Yi
HY
Lee
Laboratory of Epigenetics and Cancer Stem Cells, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, China; Graduate Institute of Life Sciences, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, China.
Yu-Ping
YP
Liao
Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, China.
Tai-Kuang
TK
Chao
Laboratory of Epigenetics and Cancer Stem Cells, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, China; Graduate Institute of Medical Sciences, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, China.
Po-Hsuan
PH
Su
Laboratory of Epigenetics and Cancer Stem Cells, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, China; Graduate Institute of Medical Sciences, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, China; Department of Obstetrics and Gynecology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, China; Graduate Institute of Life Sciences, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, China. Electronic address: hclai@ndmctsgh.edu.tw.
Hung-Cheng
HC
Lai
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000080924:Aldehyde Dehydrogenase 1 Family; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000201:enzymology / Q000401:mortality; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy / Q000201:enzymology* / Q000401:mortality; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism* / Q000401:mortality; D050697:Retinal Dehydrogenase / Q000378:metabolism*; D018874:Spheroids, Cellular; D023041:Xenograft Model Antitumor Assays; D055815:Young Adult
D014408:Biomarkers, Tumor; D018960:Hyaluronan Receptors; D007527:Isoenzymes; D000080924:Aldehyde Dehydrogenase 1 Family; C510223:ALDH1A1 protein, human; C515028:ALDH1A1 protein, mouse; D050697:Retinal Dehydrogenase