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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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Autores principales: Nagaraj, Vini, Mikhail, Mirai, Baronio, Micol, Gatto, Alessia, Nayak, Ashana, Theis, Thomas, Cavallaro, Ugo, Schachner, Melitta
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8946856/
https://www.ncbi.nlm.nih.gov/pubmed/35327631
http://dx.doi.org/10.3390/biom12030439
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author Nagaraj, Vini
Mikhail, Mirai
Baronio, Micol
Gatto, Alessia
Nayak, Ashana
Theis, Thomas
Cavallaro, Ugo
Schachner, Melitta
author_facet Nagaraj, Vini
Mikhail, Mirai
Baronio, Micol
Gatto, Alessia
Nayak, Ashana
Theis, Thomas
Cavallaro, Ugo
Schachner, Melitta
author_sort Nagaraj, Vini
collection PubMed
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.
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spelling pubmed-89468562022-03-25 Antagonistic L1 Adhesion Molecule Mimetic Compounds Inhibit Glioblastoma Cell Migration In Vitro Nagaraj, Vini Mikhail, Mirai Baronio, Micol Gatto, Alessia Nayak, Ashana Theis, Thomas Cavallaro, Ugo Schachner, Melitta Biomolecules Article 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. MDPI 2022-03-12 /pmc/articles/PMC8946856/ /pubmed/35327631 http://dx.doi.org/10.3390/biom12030439 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Nagaraj, Vini
Mikhail, Mirai
Baronio, Micol
Gatto, Alessia
Nayak, Ashana
Theis, Thomas
Cavallaro, Ugo
Schachner, Melitta
Antagonistic L1 Adhesion Molecule Mimetic Compounds Inhibit Glioblastoma Cell Migration In Vitro
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 Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8946856/
https://www.ncbi.nlm.nih.gov/pubmed/35327631
http://dx.doi.org/10.3390/biom12030439
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