Introduction/Background*Adult granulosa cell tumors (AGCT) accounting about 95% GCT (granulosa cell tumors) is characterized by the occurrence of an aggressive form and frequent appearance of recurrence and metastasis (1). Furthermore, reports indicated that the level of visfatin, which is one of adipokine, is elevated in ascites fluid of ovarian cancer patients with diagnosed metastases (2). Moreover, the role of visfatin in cancer metabolic reprogramming was demonstrated (3). Therefore, the aim of this research is to determine whether visfatin by reprogramming metabolism may be involved in invasion of AGCT
Methodology Human AGCT-derived cell line KGN (Riken Cell Bank) was cultured in three-dimensional culture. Spheroids were exposed to visfatin (100 ng/ml) for 24 h and invasion was measured using Culturex Spheroid Invasion Matrix (#3500-096-03; Trevigen). Glucose uptake was tested using a Glucose Uptake-Glo Assay (Promega) after treatment with visfatin (100 ng/ml) for 24h. Silencing of NAMPT (visfatin gene) was carried out using siRNA (SMART pool siRNA NAMPT; L-004581-00-0005) and basal glycolysis was measured using Seahorse Glycolytic Rate Assay (Agilent).
Result(s)*Firstly, we showed that visfatin increases KGN cells spheroids invasion. Furthermore, we observed stimulating glucose uptake in KGN cells after treatment with visfatin. Whereas the use of STF-31 (a blocker for the GLUT1 and an inhibitor of visfatin) abolished the stimulating effect of visfatin on the invasion, which indicates the important role of glucose metabolism in this process. Moreover, silencing of NAMPT decreased basal glycolysis in KGN cells spheroids.
Conclusion*These results stated that visfatin by reprogramming glucose metabolism plays an important role in increasing the ability of AGCT to invasion and because of that it can be a factor to progression of this cancer.
This study was funded by the National Science Centre (NCN) Poland (grant number 2019/33/N/NZ5/00471)
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