title: Aldehyde dehydrogenase 1 identifies cells with cancer stem cell-like properties in a human renal cell carcinoma cell line.
abstract: Cancer stem cells (CSC) or cancer stem cell-like cells (CSC-LCs) have been identified in many malignant tumors. CSCs are proposed to be related with drug resistance, tumor recurrence, and metastasis and are considered as a new target for cancer treatment; however, there are only a few reports on CSCs or CSC-LCs in renal cell carcinoma (RCC). Different approaches have been reported for CSC identification, but there are no universal markers for CSC. We used two different approaches, the traditional side population (SP) approach, and the enzymatic (aldehyde dehydrogenase 1 (ALDH1)) approach to identify CSC-LC population in two RCC cell lines, ACHN and KRC/Y. We found that ACHN and KRC/Y contain 1.4% and 1.7% SP cells, respectively. ACHN SP cells showed a higher sphere forming ability, drug resistance, and a slightly higher tumorigenic ability in NOD/SCID mice than Non-SP (NSP) cells, suggesting that cells with CSC-LC properties are included in ACHN SP cells. KRC/Y SP and NSP cells showed no difference in such properties. ALDH1 activity analysis revealed that ACHN SP cells expressed a higher level of activity than NSP cells (SP vs. NSP: 32.7% vs 14.6%). Analysis of ALDH1-positive ACHN cells revealed that they have a higher sphere forming ability, self-renewal ability, tumorigenicity and express higher mRNA levels of CSC-LC property-related genes (e.g., ABC transporter genes, self-replication genes, anti-apoptosis genes, and so forth) than ALDH1-negative cells. Drug treatment or exposure to hypoxic condition induced a 2- to 3-fold increase in number of ALDH1-positive cells. In conclusion, the results suggest that the ALDH1-positive cell population rather than SP cells show CSC-LC properties in a RCC cell line, ACHN.
authors.affiliation: Department of Pathology, Kurume University School of Medicine, Kurume, Fukuoka, Japan ; Department of Urology, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Ueda
authors.forename: Sachiko
authors.initials: S
authors.lastname: Ogasawara
authors.forename: Jun
authors.initials: J
authors.lastname: Akiba
authors.forename: Masamichi
authors.initials: M
authors.lastname: Nakayama
authors.forename: Keita
authors.initials: K
authors.lastname: Todoroki
authors.forename: Keiko
authors.initials: K
authors.lastname: Ueda
authors.forename: Sakiko
authors.initials: S
authors.lastname: Sanada
authors.forename: Shigetaka
authors.initials: S
authors.lastname: Suekane
authors.forename: Masanori
authors.initials: M
authors.lastname: Noguchi
authors.forename: Kei
authors.initials: K
authors.lastname: Matsuoka
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Yano
mesh_terms: D000080924:Aldehyde Dehydrogenase 1 Family; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D063646:Carcinogenesis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D050697:Retinal Dehydrogenase / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D007527:Isoenzymes; D000080924:Aldehyde Dehydrogenase 1 Family; C510223:ALDH1A1 protein, human; C515028:ALDH1A1 protein, mouse; D050697:Retinal Dehydrogenase