Abstract
Angiogenesis involves a number of different players among which extracellular nanovesicles (EVs) have recently been proposed as an efficient cargo of pro-angiogenic mediators. Angiogenesis plays a key role in osteosarcoma (OS) development and progression. Acidity is a hallmark of malignancy in a variety of cancers, including sarcomas, as a result of an increased energetic metabolism. The aim of this study was to investigate the role of EVs derived from osteosarcoma cells on angiogenesis and whether extracellular acidity, generated by tumor metabolism, could influence EVs activity. For this purpose, we purified and characterized EVs from OS cells maintained at either acidic or neutral pH. The ability of EVs to induce angiogenesis was assessed in vitro by endothelial cell tube formation and in vivo using chicken chorioallantoic membrane. Our findings demonstrated that EVs derived from osteosarcoma cells maintained either in acidic or neutral conditions induced angiogenesis. The results showed that miRNA and protein content of EVs cargo are correlated with pro-angiogenic activity and this activity is increased by the acidity of tumor microenvironment. This study provides evidence that EVs released by human osteosarcoma cells act as carriers of active angiogenic stimuli that are able to promote endothelial cell functions relevant to angiogenesis.
Highlights
Angiogenesis is a pivotal process in osteosarcoma (OS) development and progression [1,2].several anti-angiogenic compounds have been considered in preclinical experiments and clinical trials in an attempt to improve the dismal prognosis of high-grade OS patients
Several anti-angiogenic compounds have been considered in preclinical experiments and clinical trials in an attempt to improve the dismal prognosis of high-grade OS patients
We explored the hypothesis that osteosarcoma induced extracellular acidity may prompt extracellular nanovesicles (EVs) release and modify their pro-angiogenic activity
Summary
Angiogenesis is a pivotal process in osteosarcoma (OS) development and progression [1,2].several anti-angiogenic compounds have been considered in preclinical experiments and clinical trials in an attempt to improve the dismal prognosis of high-grade OS patients. The treatments showed some form of activity, they did not significantly improve the prognosis of patients.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
