Osteosarcoma tissue-engineered model challenges oxidative stress therapy revealing promoted cancer stem cell properties
The use of oxidative stress generated by Cold Atmospheric Plasma (CAP) in oncology is being recently studied as a novel potential anti-cancer therapy. However, the beneficial effects of CAP for treating osteosarcoma have mostly been demonstrated in 2-dimensional cultures of cells, which do not mimic...
| Autores: | , , , , |
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| Tipo de documento: | artigo |
| Data de publicação: | 2021 |
| País: | España |
| Recursos: | Universitat Politècnica de Catalunya (UPC) |
| Repositório: | UPCommons. Portal del coneixement obert de la UPC |
| Idioma: | inglês |
| OAI Identifier: | oai:upcommons.upc.edu:2117/335727 |
| Acesso em linha: | https://hdl.handle.net/2117/335727 https://dx.doi.org/10.1016/j.freeradbiomed.2020.12.437 |
| Access Level: | Acceso aberto |
| Palavra-chave: | Cold atmospheric plasma Plasma activated liquids Osteosarcoma Cancer stem-like cells 3D tumor model Oxidative stress Reactive oxygen and nitrogen species Plasma Càncer d'ossos Àrees temàtiques de la UPC::Enginyeria biomèdica::Biomaterials |
| Resumo: | The use of oxidative stress generated by Cold Atmospheric Plasma (CAP) in oncology is being recently studied as a novel potential anti-cancer therapy. However, the beneficial effects of CAP for treating osteosarcoma have mostly been demonstrated in 2-dimensional cultures of cells, which do not mimic the complexity of the 3-dimensional (3D) bone microenvironment. In order to evaluate the effects of CAP in a relevant context of the human disease, we developed a 3D tissue-engineered model of osteosarcoma using a bone-like scaffold made of collagen type I and hydroxyapatite nanoparticles. Human osteosarcoma cells cultured within the scaffold showed a high capacity to infiltrate and proliferate and to exhibit osteomimicry in vitro. As expected, we observed significantly different functional behaviors between monolayer and 3D cultures when treated with Cold Plasma-Activated Ringer's Solution (PAR). Our data reveal that the 3D environment not only protects cells from PAR-induced lethality by scavenging and diminishing the amount of reactive oxygen and nitrogen species generated by CAP, but also favours the stemness phenotype of osteosarcoma cells. This is the first study that demonstrates the negative effect of PAR on cancer stem-like cell subpopulations in a 3D biomimetic model of cancer. These findings will allow to suitably re-focus research on plasma-based therapies in future. |
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