L1 cell adhesion molecule confers radioresistance to ovarian cancer and defines a new cancer stem cell population

• Verfasst von: Terraneo, Nastassja [VerfasserIn]
• Verfasst von: Peitzsch, Claudia [VerfasserIn]
• Titel: L1 cell adhesion molecule confers radioresistance to ovarian cancer and defines a new cancer stem cell population
• Verf.angabe: Nastassja Terraneo, Francis Jacob, Claudia Peitzsch, Anna Dubrovska, Christiane Krudewig, Yen-Lin Huang, Viola Heinzelmann-Schwarz, Roger Schibli, Martin Béhé and Jürgen Grünberg
• E-Jahr: 2020
• Jahr: 15 January 2020
• Umfang: 17 S.
• Fussnoten: Gesehen am 08.07.2020
• Titel Quelle: Enthalten in: Cancers
• Ort Quelle: Basel : MDPI, 2009
• Jahr Quelle: 2020
• Band/Heft Quelle: 12(2020,1) Artikel-Nummer 217, 17 Seiten
• ISSN Quelle: 2072-6694
• DOI: doi:10.3390/cancers12010217
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: CRISPR-Cas9
• Sach-SW: epithelial-to-mesenchymal transition
• Sach-SW: L1 cell adhesion molecule
• Sach-SW: ovarian cancer
• Sach-SW: radioresistance
• Sach-SW: stem cells
• K10plus-PPN: 1696961424

Abstract

Many solid tumors, including ovarian cancer, contain small populations of cancer stem cells (CSCs). These cells are usually resistant against conventional cancer therapies and play a role in disease recurrence. We demonstrated that the L1 cell adhesion molecule (L1CAM) is a new CSC target in ovarian cancer, triggering radioresistance. Using fluorescence-activated cell sorting, specific cell populations expressing L1CAM alone or in combination with the established CSC marker CD133 were isolated from three ovarian cancer cell lines. Double-positive L1CAM+/CD133+ cells displayed higher spherogenic and clonogenic properties in comparison to L1CAM−/CD133− cells. Furthermore, L1CAM+/CD133+ cells retained highest clonogenic capacity after irradiation and exhibited up-regulation of some CSC-specific genes, enhanced tumor-initiating capacity, self-renewal and higher tumor take rate in nude mice when compared with other cell populations. Superior radioresistance by L1CAM expression was confirmed by deletion of L1CAM using CRISPR-Cas9 technology. Moreover, we found expression signatures associated with epithelial-to-mesenchymal transition phenotype in L1CAM deleted cells. These results indicate that L1CAM in combination with CD133 defines a new cancer cell population of ovarian tumor-initiating cells with the implication of targeting L1CAM as a novel therapeutic approach for ovarian CSCs.