Next Article in Journal
Plasma Membrane Ca2+ ATPase Isoform 4 (PMCA4) Has an Important Role in Numerous Hallmarks of Pancreatic Cancer
Previous Article in Journal
Aptamer-Conjugated Superparamagnetic Ferroarabinogalactan Nanoparticles for Targeted Magnetodynamic Therapy of Cancer
Open AccessArticle

L1 Cell Adhesion Molecule Confers Radioresistance to Ovarian Cancer and Defines a New Cancer Stem Cell Population

1
Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, 5232 Villigen-PSI, Switzerland
2
Ovarian Cancer Research, Department of Biomedicine, University Hospital Basel and University of Basel, 4031 Basel, Switzerland
3
National Center for Tumor Diseases (NCT), Partner Site Dresden, 01307 Dresden, Germany
4
German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
5
OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany
6
German Cancer Consortium (DKTK), Partner site Dresden, 01307 Dresden, Germany
7
Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiooncology-OncoRay, 01307 Dresden, Germany
8
Laboratory for Animal Model Pathology (LAMP), Institute of Veterinary Pathology, Vetsuisse Faculty, University of Zurich, 8057 Zurich, Switzerland
9
Hospital for Women, University Hospital Basel, 4031 Basel, Switzerland
10
Department of Chemistry and Applied Biosciences, ETH Zurich, 8093 Zurich, Switzerland
*
Author to whom correspondence should be addressed.
Cancers 2020, 12(1), 217; https://doi.org/10.3390/cancers12010217
Received: 25 November 2019 / Revised: 18 December 2019 / Accepted: 12 January 2020 / Published: 15 January 2020
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.
Keywords: L1 cell adhesion molecule; ovarian cancer; stem cells; radioresistance; CRISPR-Cas9; epithelial-to-mesenchymal transition L1 cell adhesion molecule; ovarian cancer; stem cells; radioresistance; CRISPR-Cas9; epithelial-to-mesenchymal transition
MDPI and ACS Style

Terraneo, N.; Jacob, F.; Peitzsch, C.; Dubrovska, A.; Krudewig, C.; Huang, Y.-L.; Heinzelmann-Schwarz, V.; Schibli, R.; Béhé, M.; Grünberg, J. L1 Cell Adhesion Molecule Confers Radioresistance to Ovarian Cancer and Defines a New Cancer Stem Cell Population. Cancers 2020, 12, 217.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop