Distinct expression levels and patterns of stem cell marker, aldehyde dehydrogenase isoform 1 (ALDH1), in human epithelial cancers.
Aldehyde dehydrogenase isoform 1 (ALDH1) has been proved useful for the identification of cancer stem cells. However, our knowledge of the expression and activity of ALDH1 in common epithelial cancers and their corresponding normal tissues is still largely absent. Therefore, we characterized ALDH1 expression in 24 types of normal tissues and a large collection of epithelial tumor specimens (six cancer types, n = 792) by immunohistochemical staining. Using the ALDEFUOR assay, ALDH1 activity was also examined in 16 primary tumor specimens and 43 established epithelial cancer cell lines. In addition, an ovarian cancer transgenic mouse model and 7 murine ovarian cancer cell lines were analyzed. We found that the expression levels and patterns of ALDH1 in epithelial cancers are remarkably distinct, and they correlate with their corresponding normal tissues. ALDH1 protein expression levels are positively correlated with ALDH1 enzymatic activity measured by ALDEFLUOR assay. Long-term in vitro culture doesn't significantly affect ALDH1 activity in epithelial tumor cells. Consistent with research on other cancers, we found that high ALDH1 expression is significantly associated with poor clinical outcomes in serous ovarian cancer patients (n = 439, p = 0.0036). Finally, ALDH(br) tumor cells exhibit cancer stem cell properties and are resistant to chemotherapy. As a novel cancer stem cell marker, ALDH1 can be used for tumors whose corresponding normal tissues express ALDH1 in relatively restricted or limited levels such as breast, lung, ovarian or colon cancer.
Deng
Shan
S
Center for Research on Early Detection and Cure of Ovarian Cancer, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
Yang
Xiaojun
X
Lassus
Heini
H
Liang
Shun
S
Kaur
Sippy
S
Ye
Qunrui
Q
Li
Chunsheng
C
Wang
Li-Ping
LP
Roby
Katherine F
KF
Orsulic
Sandra
S
Connolly
Denise C
DC
Zhang
Youcheng
Y
Montone
Kathleen
K
Bützow
Ralf
R
Coukos
George
G
Zhang
Lin
L
D000080924:Aldehyde Dehydrogenase 1 Family; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D002277:Carcinoma / Q000175:diagnosis* / Q000201:enzymology; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000201:enzymology*; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000032:analysis*; D051379:Mice; D008822:Mice, Transgenic; D014411:Neoplastic Stem Cells / Q000201:enzymology*; D010051:Ovarian Neoplasms / Q000473:pathology; D011379:Prognosis; D050697:Retinal Dehydrogenase / Q000032:analysis*
D015415:Biomarkers; D007527:Isoenzymes; D000080924:Aldehyde Dehydrogenase 1 Family; C510223:ALDH1A1 protein, human; C515028:ALDH1A1 protein, mouse; D050697:Retinal Dehydrogenase