β-endorphin at the intersection of pain and cancer progression: Preclinical evidence

Donovan A. Argueta, Anupam Aich, Jianxun Lei, Stacy Kiven, Aithanh Nguyen, Ying Wang, Joshua Gu, Weian Zhao, Kalpna Gupta

Research output: Contribution to journalArticlepeer-review

Abstract

We examined the association between endogenous opioid β-endorphin, cancer progression and pain in a transgenic mouse model of breast cancer, with a rat C3(1) simian virus 40 large tumor antigen fusion gene (C3TAg). C3TAg mice develop ductal epithelial atypia at 8 weeks, progression to intra-epithelial neoplasia at 12 weeks, and invasive carcinoma with palpable tumors at 16 weeks. Consistent with invasive carcinoma at 4 months of age, C3TAg mice demonstrate a significant increase in hyperalgesia compared to younger C3TAg or control FVBN mice without tumors. Our data show that the growing tumor contributes to circulating β-endorphin. As an endogenous ligand of mu opioid receptor, β-endorphin has analgesic activity. Paradoxically, we observed an increase in pain in transgenic breast cancer mice with significantly high circulating and tumor-associated β-endorphin. Increased circulating β-endorphin correlates with increasing tumor burden. β-endorphin induced the activation of mitogenic and survival-promoting signaling pathways, MAPK/ERK 1/2, STAT3 and Akt, observed by us in human MDA-MB-231 cells suggesting a role for β-endorphin in breast cancer progression and associated pain.

Original languageEnglish (US)
Article number135601
JournalNeuroscience Letters
Volume744
DOIs
StatePublished - Jan 23 2021
Externally publishedYes

Bibliographical note

Funding Information:
This work has been supported by NIH grants, UO1 HL117664 , RO1 HL147562 , U18 EB029354 to KG; a Diversity Supplement 3R01HL147562-03S to SK, University of California President’s Fellowship to DAA and University of California Provost’s Research Growth Fund Award to WZ and KG. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Publisher Copyright:
© 2020 Elsevier B.V.

Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.

Keywords

  • Breast cancer
  • Morphine
  • Opioid
  • Pain
  • β-Endorphin

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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