Antagonistic L1 Adhesion Molecule Mimetic Compounds Inhibit Glioblastoma Cell Migration In Vitro
Cell adhesion molecule L1 is a cell surface glycoprotein that promotes neuronal cell migration, fosters regeneration after spinal cord injury and ameliorates the consequences of neuronal degeneration in mouse and zebrafish models. Counter-indicative features of L1 were found in tumor progression: th...
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| Format: | Article |
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MDPI AG
2022-03-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/12/3/439 |
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| author | Vini Nagaraj Mirai Mikhail Micol Baronio Alessia Gatto Ashana Nayak Thomas Theis Ugo Cavallaro Melitta Schachner |
| author_facet | Vini Nagaraj Mirai Mikhail Micol Baronio Alessia Gatto Ashana Nayak Thomas Theis Ugo Cavallaro Melitta Schachner |
| author_sort | Vini Nagaraj |
| collection | DOAJ |
| description | Cell adhesion molecule L1 is a cell surface glycoprotein that promotes neuronal cell migration, fosters regeneration after spinal cord injury and ameliorates the consequences of neuronal degeneration in mouse and zebrafish models. Counter-indicative features of L1 were found in tumor progression: the more L1 is expressed, the more tumor cells migrate and increase their metastatic potential. L1′s metastatic potential is further evidenced by its promotion of epithelial–mesenchymal transition, endothelial cell transcytosis and resistance to chemo- and radiotherapy. These unfortunate features are indicated by observations that cells that normally do not express L1 are induced to express it when becoming malignant. With the aim to ameliorate the devastating functions of L1 in tumors, we designed an alternative approach to counteract tumor cell migration. Libraries of small organic compounds were screened using the ELISA competition approach similar to the one that we used for identifying L1 agonistic mimetics. Whereas in the former approach, a function-triggering monoclonal antibody was used for screening libraries, we here used the function-inhibiting monoclonal antibody 324 that reduces the migration of neurons. We now show that the L1 antagonistic mimetics anagrelide, 2-hydroxy-5-fluoropyrimidine and mestranol inhibit the migration of cultured tumor cells in an L1-dependent manner, raising hopes for therapy. |
| first_indexed | 2024-03-09T20:04:50Z |
| format | Article |
| id | doaj.art-6facbcba1e0d4586a0fb15f0cd518e1b |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-09T20:04:50Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-6facbcba1e0d4586a0fb15f0cd518e1b2023-11-24T00:35:52ZengMDPI AGBiomolecules2218-273X2022-03-0112343910.3390/biom12030439Antagonistic L1 Adhesion Molecule Mimetic Compounds Inhibit Glioblastoma Cell Migration In VitroVini Nagaraj0Mirai Mikhail1Micol Baronio2Alessia Gatto3Ashana Nayak4Thomas Theis5Ugo Cavallaro6Melitta Schachner7Keck Center for Collaborative Neuroscience, Department of Cell Biology and Neuroscience, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USAKeck Center for Collaborative Neuroscience, Department of Cell Biology and Neuroscience, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USAUnit of Gynaecological Oncology Research, European Institute of Oncology IRCSS, 20139 Milan, ItalyUnit of Gynaecological Oncology Research, European Institute of Oncology IRCSS, 20139 Milan, ItalyKeck Center for Collaborative Neuroscience, Department of Cell Biology and Neuroscience, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USAKeck Center for Collaborative Neuroscience, Department of Cell Biology and Neuroscience, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USAUnit of Gynaecological Oncology Research, European Institute of Oncology IRCSS, 20139 Milan, ItalyKeck Center for Collaborative Neuroscience, Department of Cell Biology and Neuroscience, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USACell adhesion molecule L1 is a cell surface glycoprotein that promotes neuronal cell migration, fosters regeneration after spinal cord injury and ameliorates the consequences of neuronal degeneration in mouse and zebrafish models. Counter-indicative features of L1 were found in tumor progression: the more L1 is expressed, the more tumor cells migrate and increase their metastatic potential. L1′s metastatic potential is further evidenced by its promotion of epithelial–mesenchymal transition, endothelial cell transcytosis and resistance to chemo- and radiotherapy. These unfortunate features are indicated by observations that cells that normally do not express L1 are induced to express it when becoming malignant. With the aim to ameliorate the devastating functions of L1 in tumors, we designed an alternative approach to counteract tumor cell migration. Libraries of small organic compounds were screened using the ELISA competition approach similar to the one that we used for identifying L1 agonistic mimetics. Whereas in the former approach, a function-triggering monoclonal antibody was used for screening libraries, we here used the function-inhibiting monoclonal antibody 324 that reduces the migration of neurons. We now show that the L1 antagonistic mimetics anagrelide, 2-hydroxy-5-fluoropyrimidine and mestranol inhibit the migration of cultured tumor cells in an L1-dependent manner, raising hopes for therapy.https://www.mdpi.com/2218-273X/12/3/439L1CAMCD171small compound librariesmonoclonal L1 antibody 324antagonist mimeticsmigration |
| spellingShingle | Vini Nagaraj Mirai Mikhail Micol Baronio Alessia Gatto Ashana Nayak Thomas Theis Ugo Cavallaro Melitta Schachner Antagonistic L1 Adhesion Molecule Mimetic Compounds Inhibit Glioblastoma Cell Migration In Vitro Biomolecules L1CAM CD171 small compound libraries monoclonal L1 antibody 324 antagonist mimetics migration |
| title | Antagonistic L1 Adhesion Molecule Mimetic Compounds Inhibit Glioblastoma Cell Migration In Vitro |
| title_full | Antagonistic L1 Adhesion Molecule Mimetic Compounds Inhibit Glioblastoma Cell Migration In Vitro |
| title_fullStr | Antagonistic L1 Adhesion Molecule Mimetic Compounds Inhibit Glioblastoma Cell Migration In Vitro |
| title_full_unstemmed | Antagonistic L1 Adhesion Molecule Mimetic Compounds Inhibit Glioblastoma Cell Migration In Vitro |
| title_short | Antagonistic L1 Adhesion Molecule Mimetic Compounds Inhibit Glioblastoma Cell Migration In Vitro |
| title_sort | antagonistic l1 adhesion molecule mimetic compounds inhibit glioblastoma cell migration in vitro |
| topic | L1CAM CD171 small compound libraries monoclonal L1 antibody 324 antagonist mimetics migration |
| url | https://www.mdpi.com/2218-273X/12/3/439 |
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