L1 cell adhesion molecule confers radioresistance to ovarian cancer and defines a new cancer stem cell population
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...
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| Main Authors: | , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
15 January 2020
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| In: |
Cancers
Year: 2020, Volume: 12, Issue: 1 |
| ISSN: | 2072-6694 |
| DOI: | 10.3390/cancers12010217 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.3390/cancers12010217 Verlag, lizenzpflichtig, Volltext: https://www.mdpi.com/2072-6694/12/1/217 
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| Author Notes: | Nastassja Terraneo, Francis Jacob, Claudia Peitzsch, Anna Dubrovska, Christiane Krudewig, Yen-Lin Huang, Viola Heinzelmann-Schwarz, Roger Schibli, Martin Béhé and Jürgen Grünberg |
| Summary: | 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. |
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| Item Description: | Gesehen am 08.07.2020 |
| Physical Description: | Online Resource |
| ISSN: | 2072-6694 |
| DOI: | 10.3390/cancers12010217 |