Heparanase accelerates the angiogenesis and inhibits the ferroptosis of p53-mutant non-small cell cancers in VEGF-dependent manner.

The aim of this study is to explore the effects and specific mechanisms of heparanase on angiogenesis and iron deficiency anemia in TP53 mutant cancer. For this purpose, we conducted in vitro cell experiments and in vivo animal experiments respectively. In this study, we first analyzed the differential expression of heparanase in TP53 wild-type and mutant cells, and analyzed its effects on iron removal and angiogenesis in two types of CALU-1 and NCI-H358 cells. Secondly, we validated whether the mechanism of action of heparanase on TP53 mutant cells for iron removal and angiogenesis is related to VEGF. We applied the iron removal agonist erastin and VEGF inhibitor bevacizumab in both in vitro and in vivo experiments to validate the relationship between heparanase and VEGF in the mechanisms of iron removal and angiogenesis. The experimental results show that heparanase is highly expressed in TP53 mutated cancer cells, and has anti-ferroptosis and pro-angiogenic effects. Our experiment also confirmed that the effect of heparanase on TP53 mutant cancer's iron removal and angiogenesis is related to VEGF. In short, heparanase is highly expressed in p53 mutated lung cancer, and the mechanism of ferroptosis tolerance to TP53 mutated cancer is related to VEGF.