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

Reproductive Sciences volume 28, pages 1012–1019 (2021)Cite this article

Abstract

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.

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Abbreviations

EM:

Endometriosis

KS:

Kallistatin

EuESCs:

Eutopic endometrium cells

EESCs:

Ectopic endometrium cells

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Acknowledgments

This study was supported by the National Nature Science Foundation of China, Grant Numbers: 81701414, 81871211.

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Author notes

  1. Yuling Mao and Jingda Qiao contributed equally to this work.

Affiliations

  1. Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, 63Duobao Road, Guangzhou, 510150, China

    Yuling Mao, Shiping Chen, Xueliang Zhou, Lei Li & Yang Luo

  2. Key Laboratory for Reproductive Medicine of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, People’s Republic of China

    Yuling Mao, Shiping Chen, Xueliang Zhou, Lei Li & Yang Luo

  3. Institute of Neuroscience and Department of Neurology of the Second Affiliated Hospital of Guangzhou Medical University, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510260, China

    Jing-Da Qiao

  4. Department of Clinical Laboratory, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China

    Zheng Wang

  5. Department of Anatomy, Histology and Developmental Biology, School of Basic Medical Sciences, Shenzhen University Health Science Centre, Shenzhen, 518060, China

    Song Cai

Authors
  1. Yuling Mao
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  2. Jing-Da Qiao
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  3. Shiping Chen
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  4. Xueliang Zhou
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  6. Song Cai
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  7. Lei Li
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  8. Yang Luo
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Correspondence to Lei Li or Yang Luo.

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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

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  • DOI: https://doi.org/10.1007/s43032-020-00421-1

Keywords

  • Anoikis
  • Kallistatin
  • Endometriosis