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Int J Mol Sci ; 25(9)2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38732030

RESUMO

Melanoma, the deadliest type of skin cancer, has a high propensity to metastasize to other organs, including the brain, lymph nodes, lungs, and bones. While progress has been made in managing melanoma with targeted and immune therapies, many patients do not benefit from these current treatment modalities. Tumor cell migration is the initial step for invasion and metastasis. A better understanding of the molecular mechanisms underlying metastasis is crucial for developing therapeutic strategies for metastatic diseases, including melanoma. The cell adhesion molecule L1CAM (CD171, in short L1) is upregulated in many human cancers, enhancing tumor cell migration. Earlier studies showed that the small-molecule antagonistic mimetics of L1 suppress glioblastoma cell migration in vitro. This study aims to evaluate if L1 mimetic antagonists can inhibit melanoma cell migration in vitro and in vivo. We showed that two antagonistic mimetics of L1, anagrelide and 2-hydroxy-5-fluoropyrimidine (2H5F), reduced melanoma cell migration in vitro. In in vivo allograft studies, only 2H5F-treated female mice showed a decrease in tumor volume.


Assuntos
Movimento Celular , Melanoma , Molécula L1 de Adesão de Célula Nervosa , Animais , Feminino , Humanos , Camundongos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Melanoma/tratamento farmacológico , Melanoma/metabolismo , Melanoma/patologia , Molécula L1 de Adesão de Célula Nervosa/metabolismo , Pirimidinas/farmacologia , Pirimidinas/uso terapêutico , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , Quinazolinas/farmacologia , Quinazolinas/uso terapêutico
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