PD43-10 CANCER-ASSOCIATED ADIPOSE-DERIVED MESENCHYMAL STEM CELLS PROMOTE MIGRATION AND INVASION IN KIDNEY CANCER

Abstract

You have accessJournal of UrologyCME1 May 2022PD43-10 CANCER-ASSOCIATED ADIPOSE-DERIVED MESENCHYMAL STEM CELLS PROMOTE MIGRATION AND INVASION IN KIDNEY CANCER Yumina Muto, Kazuyuki Numakura, Yuya Sekine, Mizuki Kobayashi, Soki Kashima, Ryohei Yamamoto, Atsushi Koizumi, Taketoshi Nara, Mitsuru Saito, Shintaro Narita, Yasufumi Omori, and Tomonori Habuchi Yumina MutoYumina Muto More articles by this author , Kazuyuki NumakuraKazuyuki Numakura More articles by this author , Yuya SekineYuya Sekine More articles by this author , Mizuki KobayashiMizuki Kobayashi More articles by this author , Soki KashimaSoki Kashima More articles by this author , Ryohei YamamotoRyohei Yamamoto More articles by this author , Atsushi KoizumiAtsushi Koizumi More articles by this author , Taketoshi NaraTaketoshi Nara More articles by this author , Mitsuru SaitoMitsuru Saito More articles by this author , Shintaro NaritaShintaro Narita More articles by this author , Yasufumi OmoriYasufumi Omori More articles by this author , and Tomonori HabuchiTomonori Habuchi More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002604.10AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Adipose-derived mesenchymal stem cells (A-MSCs) are known to be a preeminent contributor to tumor microenvironments. Their role in renal cell carcinoma (RCC) has not been entirely investigated. This study aimed to clarify the significance of A-MSCs in RCC. METHODS: Human A-MSCs were isolated from the perirenal fat in RCC patients (RCC-MSC) and kidney transplantation donors (Donor-MSC) for use as controls. Several RCC cell lines were co-cultured with the A-MSCs, then analyzed for their migration and invasive ability. Molecular pathways activated in the RCC-MSCs and isolated RCC cultures were assessed. Beta-catenin in perirenal fat from surgical specimens from RCC patients was stained by immunohistochemistry (IHC). RESULTS: RCC-MSCs expressed higher levels of mRNAs encoding Hes1, Hey1, and Twist, higher protein levels of beta-catenin, and reduced protein levels of phospho-Akt (Ser473) and phospho-p38 MAPK relative to Donor-MSCs (Figure 1A and B). These results suggest that RCC-MSC stemness is reduced compared with Donor-MSCs in terms of stemness associated molecular pathways. This finding was confirmed by the aldehyde dehydrogenase enzymatic activity (ALDH) assays, in which fewer RCC-MSCs were ALDH+ than Donor-MSCs (Figure 1C). We next analyzed cell function by co-culturing with RCC cell lines. Tumor cell migration was significantly elevated in RCC-MSC cultures compared with RCC cell lines cultured alone (Figure 2A and B). Pathway screening using the RCC cell line revealed elevated urokinase-type plasminogen activator (uPA) mRNA expression in RCC-MSCs than cultured alone (Figure 2C). In RCC surgical specimens, IHC of perirenal stromal tissue for beta-catenin showed a high positive correlation with tumor aggressiveness (Figure 2D). CONCLUSIONS: Co-culturing of RCC-MSCs with RCC cell lines exacerbated tumor invasiveness. Interaction between A-MSCs and tumors may promote A-MSC differentiation from pluripotent stem cells, and facilitate RCC migration and invasion by increasing expression of uPA in tumor cells. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e706 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Yumina Muto More articles by this author Kazuyuki Numakura More articles by this author Yuya Sekine More articles by this author Mizuki Kobayashi More articles by this author Soki Kashima More articles by this author Ryohei Yamamoto More articles by this author Atsushi Koizumi More articles by this author Taketoshi Nara More articles by this author Mitsuru Saito More articles by this author Shintaro Narita More articles by this author Yasufumi Omori More articles by this author Tomonori Habuchi More articles by this author Expand All Advertisement PDF DownloadLoading ...