The impact of hypoxia on KGN cells

Human granulosa cells (GCs) give rise to granulosa cell tumors (GCTs), in which a hypoxic situation can be assumed. KGN cells are a widely used cellular model for both tumorous and normal human GCs. In this study, we evaluated consequences of hypoxic (1% O2) versus atmospheric conditions on KGNs for a total of 10 days. A proteomic analysis showed 57 more and 75 less abundant proteins in hypoxia. Of these proteins, 72 overlap with the ones of GCs exposed to hypoxia (ProteomeXchange Consortium dataset identifier PXD042934). Common up-regulated pathways include cellular response to hypoxia and glucose metabolism, whereas the mitochondrial 5’-end processing pathway was significantly down-regulated in both cell types. 60 proteins were uniquely regulated in KGN cells, indicating cell-type-specific responses. This is in line with findings of nuclear expression of HIF1α in acute (2h) and prolonged (10d) hypoxia in KGNs, in contrast to its nuclear presence in GCs only in acute hypoxia. Hypoxia also affected cell number and size but not the migratory behavior of KGNs. The results provide a detailed picture of hypoxia-induced changes in KGNs and indicate that low O2 in the tumor microenvironment may have an important and multifaceted influence on GCTs.