298 IDENTIFICATION AND CHARACTERIZATION OF CANCER STEM CELL OF RENAL CELL CARCINOMA CELL LINES

Abstract

You have accessJournal of UrologyKidney Cancer: Basic Research (II)1 Apr 2013298 IDENTIFICATION AND CHARACTERIZATION OF CANCER STEM CELL OF RENAL CELL CARCINOMA CELL LINES Kosuke Ueda, Sachiko Ogasawara, Jun Akiba, Masamichi Nakayama, Sakiko Sanada, Shigetaka Suekane, Masanori Noguchi, Kei Matsuoka, and Hirohisa Yano Kosuke UedaKosuke Ueda Kurume, Japan More articles by this author , Sachiko OgasawaraSachiko Ogasawara Kurume, Japan More articles by this author , Jun AkibaJun Akiba Kurume, Japan More articles by this author , Masamichi NakayamaMasamichi Nakayama Kurume, Japan More articles by this author , Sakiko SanadaSakiko Sanada Kurume, Japan More articles by this author , Shigetaka SuekaneShigetaka Suekane Kurume, Japan More articles by this author , Masanori NoguchiMasanori Noguchi Kurume, Japan More articles by this author , Kei MatsuokaKei Matsuoka Kurume, Japan More articles by this author , and Hirohisa YanoHirohisa Yano Kurume, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.1682AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Evidence for existence of cancer stem cells (CSCs) has been reported in several malignant tumors. The population of CD105 is reported to be one of the CSC markers in renal cell carcinoma (RCC). However, there are a few reports examining the CSCs in human RCC. In our study, we isolated side population (SP) cells from the human RCC cell lines and systematically identified the CSC characteristics of the SP cells. Moreover, we examined the malignant potential with CSC like biological features of ALDH1-positive cells. METHODS We used two RCC cell lines derived from metastatic RCC (ACHN) and primary RCC (KRC/Y). The SP and Non-SP(NSP) cells were isolated from the two RCC cell lines by FACS Aria 2. We examined proliferative ability, drug resistance, clonoginity, sphere forming ability in serum-free medium in vitro and tumorigenicity in vivo between SP and NSP cells. We examined ALDH1 activity and sphere forming ability in ALDH1 expression. Moreover, we analyzed the expression of ALDH1 after treatment with Sorafenib or IFNa and exposing hypoxia. RESULTS The SP cell rates in ACHN and KRC/Y were 1.4% and 1.7%, respectively. SP cells of KRC/Y had higher cell proliferative ability and clonogenity in vitro. Although SP cells in KRC/Y expressed higher CD105-positive cell rate than NSP cells (SP vs NSP: 24.6% vs 4.6%), there was no difference in tumorigenicity in vivo. On the other hand, there was no significant difference in the cell growth rate and colony formation between SP and NSP cells in ACHN. However, the SP cells in ACHN had higher sphere forming ability and IFNa resistance in vitro and had higher tumor growth ability in vivo. The mRNA expression levels of stemness genes, HIF1a and VEGFA in isolated SP and Non-SP cells showed no significant difference. Whereas, the SP cells in ACHN expressed higher ALDH1-positive cells, which was widely known as one of the representative CSC markers, compared with NSP cells (SP vs NSP: 32.7% vs 14.6%). Furthermore, ALDH1-positive cell had higher sphere forming ability than ALDH1-negative cells. ALDH1-positive cells rate, especially treated with sorafenib or exposed in hypoxic condition, was much higher than in the control. CONCLUSIONS Cells with the features of CSC may be involved in SP cell fraction, especially in ALDH1-positive SP cell fraction. SP cells in ACHN not only overexpress ALDH1 activity but also have more resistance to the various conventional treatment for RCC. These findings may provide new insights for future CSC research and clinical anti-cancer therapy for RCC. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e121 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kosuke Ueda Kurume, Japan More articles by this author Sachiko Ogasawara Kurume, Japan More articles by this author Jun Akiba Kurume, Japan More articles by this author Masamichi Nakayama Kurume, Japan More articles by this author Sakiko Sanada Kurume, Japan More articles by this author Shigetaka Suekane Kurume, Japan More articles by this author Masanori Noguchi Kurume, Japan More articles by this author Kei Matsuoka Kurume, Japan More articles by this author Hirohisa Yano Kurume, Japan More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...