id_824. THE ROLE OF EXERCISE MIMETICS IN MODULATING THE PROANGIOGENIC PROPERTIES OF PRO-TUMORIGENIC NEUTROPHILS
Weronika Jurczyk1, Mateusz Smolarz1,2, Marta Nowacka- Chmielewska1
1 Institute of Physiotherapy and Health Sciences, Academy of Physical Education, Katowice, Poland
2 Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice, Poland
INTRODUCTION: Neutrophils constitute 50-70% of WBCs and play a significant role in modulating the tumor microenvironment. They exist in two phenotypes: anti- and pro-tumor. An important regulator of their function is the type 1 interferon receptor. Silencing this receptor promotes neutrophils to a pro-tumor phenotype (Ifnar1-/-). They can promote angiogenesis and modulate the tumor microenvironment by secreting mediators (VEGF, MMP-9). Current research indicates that small extracellular vesicles (sEVs) secreted by neutrophils may play a significant role in this modulation. Studies of exercise mimetics, including metformin and betaine, indicate that they may have anti-angiogenic and anti-tumor effects.
AIM(S): The aim of this study is to assess the potential effect of metformin and betaine on the pro-angiogenic properties of sEVs secreted by Ifnar-/- neutrophils.
METHOD(S): The study used ER-Hoxb8 progenitor cells with type 1 interferon knockout (Ifnar1-/-). To differentiate the cells into neutrophils, β-estradiol was removed from the medium 5 days prior to isolation. 48 hours before isolation the medium was changed to one with FBS depleted in exo. Isolation was performed using mini-SEC. During the differentiation period, the cells were stimulated with appropriate doses of metformin and resveratrol. Mimetics concentrations were determined based on the results of the MTT assay. The obtained sEVs were subjected to ELISA, VEGF, and MMP-9 assays.
RESULTS: The MTT assay revealed dose-dependent changes in cell viability. Based on this, optimal concentrations were selected for further testing. ELISA assays revealed a differential VEGF and MMP-9 profile in sEVs from Ifnar1-/- neutrophils treated with selected mimetics.
CONCLUSIONS: Our results suggest that mimicking the metabolic effects of physical activity using metformin and betaine may lead to changes in the proangiogenic profile of sEVs secreted by Ifna1r-/- neutrophils. This indicates a potential role of exercise-induced mechanisms in inhibiting tumorigenesis.
FINANCIAL SUPPORT: This research was funded by the NCN project: 2023/48/C/NZ5/00001