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A positive feedback loop of heparanase/syndecan1/nerve growth factor regulates cancer pain progression

  • Xiaohu, Su (Department of Anesthesiology, Suqian First People's Hospital) ;
  • Bingwu, Wang (Cancer Institute, The Second Affiliated Hospital of Xuzhou Medical University) ;
  • Zhaoyun, Zhou (Department of Anesthesiology, Tai'an Central Hospital) ;
  • Zixian, Li (Department of Anesthesiology, Graduate School of Xuzhou Medical University) ;
  • Song, Tong (Department of Anesthesiology, Graduate School of Xuzhou Medical University) ;
  • Simin, Chen (Department of Anesthesiology, Graduate School of Xuzhou Medical University) ;
  • Nan, Zhang (Department of Anesthesiology, Graduate School of Xuzhou Medical University) ;
  • Su, Liu (Department of Anesthesiology, The Affiliated Hospital of Xuzhou Medical University) ;
  • Maoyin, Zhang (Department of Anesthesiology, The Affiliated Hospital of Xuzhou Medical University)
  • Received : 2022.08.10
  • Accepted : 2022.10.22
  • Published : 2023.01.01

Abstract

Background: The purpose of this research was to assess the role of heparanase (HPSE)/syndecan1 (SDC1)/nerve growth factor (NGF) on cancer pain from melanoma. Methods: The influence of HPSE on the biological function of melanoma cells and cancer pain in a mouse model was evaluated. Immunohistochemical staining was used to analyze HPSE and SDC1. HPSE, NGF, and SDC1 were detected using western blot. Inflammatory factors were detected using ELISA assay. Results: HPSE promoted melanoma cell viability, proliferation, migration, invasion, and tumor growth, as well as cancer pain, while SST0001 treatment reversed the promoting effect of HPSE. HPSE up-regulated NGF, and NGF feedback promoted HPSE. High expression of NGF reversed the inhibitory effect of HPSE down-regulation on melanoma cell phenotype deterioration, including cell viability, proliferation, migration, and invasion. SST0001 down-regulated SDC1 expression. SDC1 reversed the inhibitory effect of SST0001 on cancer pain. Conclusions: The results showed that HPSE promoted melanoma development and cancer pain by interacting with NGF/SDC1. It provides new insights to better understand the role of HPSE in melanoma and also provides a new direction for cancer pain treatment.

Keywords

Acknowledgement

This study was supported by the project of experimental study on the role of Heparanase/Syndecan1/NGF signaling pathway and its positive feedback characteristics in the occurrence and development of cancer pain (BK20181153).

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