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A Novel Approach to Reducing Lung Metastasis in Osteosarcoma: Increasing Cell Stiffness with Carbenoxolone

Aim: 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 ther...

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Autores principales: Kita, Kouji, Asanuma, Kunihiro, Okamoto, Takayuki, Kawamoto, Eiji, Nakamura, Koichi, Hagi, Tomohito, Nakamura, Tomoki, Shimaoka, Motomu, Sudo, Akihiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10217449/
https://www.ncbi.nlm.nih.gov/pubmed/37232747
http://dx.doi.org/10.3390/cimb45050278
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author Kita, Kouji
Asanuma, Kunihiro
Okamoto, Takayuki
Kawamoto, Eiji
Nakamura, Koichi
Hagi, Tomohito
Nakamura, Tomoki
Shimaoka, Motomu
Sudo, Akihiro
author_facet Kita, Kouji
Asanuma, Kunihiro
Okamoto, Takayuki
Kawamoto, Eiji
Nakamura, Koichi
Hagi, Tomohito
Nakamura, Tomoki
Shimaoka, Motomu
Sudo, Akihiro
author_sort Kita, Kouji
collection PubMed
description Aim: 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. Methods: 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. Results: Treatment with CBX significantly increased actin staining intensity and stiffness of LM8 cells compared with vehicle-treated LM8 cells (p < 0.01). In Young’s modulus images, compared with the control group, rigid fibrillate structures were observed in the CBX treatment group. CBX suppressed cell migration, invasion, and adhesion but not cell proliferation. The number of LM8 lung metastases were significantly reduced in the CBX administration group compared with the control group (p < 0.01). Conclusion: 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.
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spelling pubmed-102174492023-05-27 A Novel Approach to Reducing Lung Metastasis in Osteosarcoma: Increasing Cell Stiffness with Carbenoxolone Kita, Kouji Asanuma, Kunihiro Okamoto, Takayuki Kawamoto, Eiji Nakamura, Koichi Hagi, Tomohito Nakamura, Tomoki Shimaoka, Motomu Sudo, Akihiro Curr Issues Mol Biol Article Aim: 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. Methods: 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. Results: Treatment with CBX significantly increased actin staining intensity and stiffness of LM8 cells compared with vehicle-treated LM8 cells (p < 0.01). In Young’s modulus images, compared with the control group, rigid fibrillate structures were observed in the CBX treatment group. CBX suppressed cell migration, invasion, and adhesion but not cell proliferation. The number of LM8 lung metastases were significantly reduced in the CBX administration group compared with the control group (p < 0.01). Conclusion: 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. MDPI 2023-05-17 /pmc/articles/PMC10217449/ /pubmed/37232747 http://dx.doi.org/10.3390/cimb45050278 Text en © 2023 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
Kita, Kouji
Asanuma, Kunihiro
Okamoto, Takayuki
Kawamoto, Eiji
Nakamura, Koichi
Hagi, Tomohito
Nakamura, Tomoki
Shimaoka, Motomu
Sudo, Akihiro
A Novel Approach to Reducing Lung Metastasis in Osteosarcoma: Increasing Cell Stiffness with Carbenoxolone
title A Novel Approach to Reducing Lung Metastasis in Osteosarcoma: Increasing Cell Stiffness with Carbenoxolone
title_full A Novel Approach to Reducing Lung Metastasis in Osteosarcoma: Increasing Cell Stiffness with Carbenoxolone
title_fullStr A Novel Approach to Reducing Lung Metastasis in Osteosarcoma: Increasing Cell Stiffness with Carbenoxolone
title_full_unstemmed A Novel Approach to Reducing Lung Metastasis in Osteosarcoma: Increasing Cell Stiffness with Carbenoxolone
title_short A Novel Approach to Reducing Lung Metastasis in Osteosarcoma: Increasing Cell Stiffness with Carbenoxolone
title_sort novel approach to reducing lung metastasis in osteosarcoma: increasing cell stiffness with carbenoxolone
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10217449/
https://www.ncbi.nlm.nih.gov/pubmed/37232747
http://dx.doi.org/10.3390/cimb45050278
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