Kallistatin Inhibits Anoikis Resistance and Metastasis of Ectopic Endometrium Cells by Modulating MnSOD and Caspase 3 Signaling

Endometriosis (EM) is a disease that involves active endometrial cell invasion and migration which is an important reason for infertility. Anoikis resistance is the most important prerequisite for EM, but the molecular mechanism is not yet clear. Kallistatin (KS) is one kind of serine protease inhibitors which had extensive biological function including anti-inflammatory, antioxidant stress, anti-angiogenesis, and anti-tumor. Our preliminary data showed that the level of KS in EM patients’ endometrial tissue and blood were much lower than control (non-EM) patients without endometriosis. Interestingly, the decrease of KS is correlated with the severity of endometriosis. Moreover, kallistatin recombinant protein could increase the anoikis rate of ectopic endometrium cells (EESCs), and then inhibits its metastasis and invasion. Mechanically, our data show that the EESCs have lower intracellular reactive oxygen species (ROS) production and KS can elevate the ROS levels significantly. Further, KS modulate expression of MnSOD and caspase 3 signaling in EESCs grown in suspended conditions. These findings reveal novel mechanisms of KS in inducing anoikis and metastasis in EESCs, thus inhibiting EM progression by regulation of MnSOD and caspase 3 signaling. Our findings suggest that KS is a significant protein with prospects for application in EM. Similar content being viewed by others Abbreviations - EM: - Endometriosis - KS: - Kallistatin - EuESCs: - Eutopic endometrium cells - EESCs: - Ectopic endometrium cells

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Author information Authors and Affiliations Corresponding authors Ethics declarations Conflict of Interests The authors declare that they have no conflict of interest. Additional information Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Rights and permissions About this article Cite this article Mao, Y., Qiao, JD., Chen, S. et al. Kallistatin Inhibits Anoikis Resistance and Metastasis of Ectopic Endometrium Cells by Modulating MnSOD and Caspase 3 Signaling. Reprod. Sci. 28, 1012–1019 (2021). https://doi.org/10.1007/s43032-020-00421-1 Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s43032-020-00421-1