A Novel Approach to Reducing Lung Metastasis in Osteosarcoma: Increasing Cell Stiffness with Carbenoxolone.
actin cytoskeleton
atomic force microscopy
carbenoxolone
cell stiffness
metastasis
Journal
Current issues in molecular biology
ISSN: 1467-3045
Titre abrégé: Curr Issues Mol Biol
Pays: Switzerland
ID NLM: 100931761
Informations de publication
Date de publication:
17 May 2023
17 May 2023
Historique:
received:
14
04
2023
revised:
08
05
2023
accepted:
15
05
2023
medline:
26
5
2023
pubmed:
26
5
2023
entrez:
26
5
2023
Statut:
epublish
Résumé
Primary malignant bone tumor osteosarcoma can metastasize to the lung. Diminishing lung metastasis would positively affect the prognosis of patients. Our previous studies demonstrated that highly metastatic osteosarcoma cell lines are significantly softer than low-metastasis cell lines. We therefore hypothesized that increasing cell stiffness would suppress metastasis by reducing cell motility. In this study, we tested whether carbenoxolone (CBX) increases the stiffness of LM8 osteosarcoma cells and prevents lung metastasis in vivo. We evaluated the actin cytoskeletal structure and polymerization of CBX-treated LM8 cells using actin staining. Cell stiffness was measured using atomic force microscopy. Metastasis-related cell functions were analyzed using cell proliferation, wound healing, invasion, and cell adhesion assays. Furthermore, lung metastasis was examined in LM8-bearing mice administered with CBX. Treatment with CBX significantly increased actin staining intensity and stiffness of LM8 cells compared with vehicle-treated LM8 cells ( In this study, we demonstrated that CBX increases tumor cell stiffness and significantly reduces lung metastasis. Our study is the first to provide evidence that reducing cell motility by increasing cell stiffness might be effective as a novel anti-metastasis approach in vivo.
Identifiants
pubmed: 37232747
pii: cimb45050278
doi: 10.3390/cimb45050278
pmc: PMC10217449
doi:
Types de publication
Journal Article
Langues
eng
Pagination
4375-4388Références
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