Abstract
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.
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The data that support the findings of this study are not publicly available due to confidentiality but are available from the corresponding author.
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This work was supported by Shandong Province Medical and Health Technology Development Plan Project (Grant Numbers 202103100394).
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All authors contributed to conceptualization. Y.S. and D.Z: material preparation, data curation and formal analysis, investigation and methodology. P.Z.: material preparation, data curation and formal analysis. N.Z.: material preparation, investigation and methodology. R.G., T.W. and F.Z.: project administration and resources. The writing of original draft was written by Y.S. and D.S. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. Each author should have participated sufficiently in the work to take public responsibility for appropriate portions of the content.
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Our animal experiments were carried out according to the institutional ethics guidelines and National Institute of Health Principles (NIH Pub.2001), and approved by the institutional Animal Care and Use Committee of Yantaishan Hospital (Ethics number: LL-2023-084-K).
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Song, Y., Zhou, D., Zhang, P. et al. Heparanase accelerates the angiogenesis and inhibits the ferroptosis of p53-mutant non-small cell cancers in VEGF-dependent manner. Cytotechnology (2024). https://doi.org/10.1007/s10616-024-00632-3
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DOI: https://doi.org/10.1007/s10616-024-00632-3