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Original research
Sonic hedgehog signaling pathway promotes pancreatic cancer pain via nerve growth factor
  1. Liang Han1,
  2. Jie Jiang2,
  3. Mengwen Xue3,
  4. Tao Qin1,
  5. Ying Xiao1,
  6. Erxi Wu4,5,
  7. Xin Shen3,
  8. Qingyong Ma1 and
  9. Jiguang Ma3
  1. 1 Department of Hepatobiliary Surgery, Xi'an Jiaotong University Medical College First Affiliated Hospital, Xi'an, Shaanxi, China
  2. 2 Department of Medical Oncology, Shaanxi Provincial People’s Hospital, Xi'an, China
  3. 3 Department of Anesthesiology, Xi'an Jiaotong University Medical College First Affiliated Hospital, Xi'an, China
  4. 4 Department of Surgery, Baylor Scott and White Health, Dallas, Texas, USA
  5. 5 Department of Neurosurgery, Baylor Scott and White Health, Dallas, Texas, USA
  1. Correspondence to Dr Qingyong Ma, Department of Hepatobiliary Surgery, Xi'an Jiaotong University Medical College First Affiliated Hospital, Xi'an, China; qyma56{at}xjtu.edu.cn

Abstract

Background Many patients with pancreatic cancer (PC) suffer from abdominal pain and back pain. However, the cause of pain associated with PC is largely unclear. In this study, we tested the potential influence of the sonic hedgehog (sHH) signaling pathway on PC pain.

Methods Substance P (SP) and calcitonin gene-related peptide (CGRP) expression was measured in cultured PC cells and dorsal root ganglions (DRG) by real-time PCR, western blotting analysis and ELISA. Small interfering RNA transfection and plasmid constructs were used to regulate the expression of sHH in the AsPc-1 and Panc-1 cell lines. Pain-related behavior was observed in an orthotopic tumor model in nude mice.

Results In this study, the results show that sHH increased the expression of SP and CGRP in DRGs in a concentration and time-dependent manner. Additionally, sHH secretion from PC cells could activate the sHH signaling pathway and, in turn, increase the expression of nerve growth factor (NGF), P75, and TrkA in DRGs. Furthermore, the sHH signaling pathway and NGF/NGF receptor contributed to pain sensitivity in a nude mouse model.

Conclusion Our results demonstrate that PC pain originates from the sHH signaling pathway, and NGF mediates the pain mechanism via regulating SP and CGRP.

  • pancreatic Cancer
  • pain
  • NGF
  • sHH
https://creativecommons.org/licenses/by/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.

https://doi.org/10.1136/rapm-2019-100991

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    Footnotes

    • LH and JJ are joint first authors.

    • Correction notice This article has been corrected since it publishe Online First. The second author affiliation has been amended.

    • Contributors Design: LH and QM. Writing: LH and JM. Analysis: JJ. Methodology: TQ, YX and MX. Data curation: EW and XS. All authors read and approved the final manuscript.

    • Funding This study was supported by the National Natural Science Foundation of China (81502074, 81672434, 81702916).

    • Competing interests None declared.

    • Patient consent for publication Not required.

    • Ethics approval The Ethical Committee of the First Affiliated Hospital of Xi’an Jiaotong University.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data availability statement Data are available in a public, open access repository. There are no data in this work. Data are available upon reasonable request. Data may be obtained from a third party and are not publicly available. All data relevant to the study are included in the article or uploaded as supplementary information.

    • Author note Corresponding author:

      Dr Qingyong Ma, Department

      of Hepatobiliary Surgery, Xi’an

      Jiaotong University Medical

      College First Affiliated Hospital,

      Xi’an, China;qyma56@ xjtu. edu. cn;

      Dr Jiguang Ma, Department of Anesthesiology,Xi’an

      Jiaotong University Medical

      College First Affiliated Hospital,

      Xi’an, China;

      jgma86{at}mail.xjtu.edu.cn