Figure 1.

The origin of HGSOC is thought to be either in the secretory cells of the fallopian tube or the ovarian surface epithelium (OSE). (A) Ovulation induces a constant damage and repair cycle in the OSE. In certain cases, these constant DNA repair cycles can cause DNA damage, leading to uncontrolled proliferation of the OSE. TNF-α and IL-1β are present in the inflammatory environment created by ovulation. They increase the expression of MMP-9 and uPA, both involved in ECM repair after ovulation, but have also been linked to HGSOC premetastatic lesions. (B) SCOUTs, an extended area of secretory cells, are thought to be the initial precursor lesion for HGSOC. SCOUTs then evolve into p53 signature, secretory cells that have developed p53 mutations. STICs are thought to be the immediate precursor lesion of HGSOC. ROS, IL-8 and IGF released during ovulation, are thought to cause increases in DNA damage leading to increased proliferation of STIC and development into HGSOC. Activated TAMs can be found in STIC lesions, secreting TGF-β, which contributes to tumor progression. TAMs are activated by p53 mutant cells within STIC lesions. Created with BioRender.com.