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

doi:10.1016/j.neulet.2020.135601

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

Neurosci Lett. 2021 Jan 23:744:135601. doi: 10.1016/j.neulet.2020.135601. Epub 2020 Dec 30.

Authors

Donovan A Argueta¹, Anupam Aich¹, Jianxun Lei², Stacy Kiven¹, Aithanh Nguyen², Ying Wang³, Joshua Gu⁴, Weian Zhao⁵, Kalpna Gupta⁶

Affiliations

¹ Hematology/Oncology, Department of Medicine, University of California, Irvine, CA, USA.
² Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
³ Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN, USA; Department of Anesthesia, Stark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA.
⁴ Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, CA, USA; Chao Family Comprehensive Cancer Center, University of California, Irvine, CA, USA; Department of Biological Chemistry, University of California, Irvine, CA, USA.
⁵ Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, CA, USA; Chao Family Comprehensive Cancer Center, University of California, Irvine, CA, USA; Department of Biological Chemistry, University of California, Irvine, CA, USA; Department of Pharmaceutical Sciences, University of California, Irvine, CA, USA; Edwards Life Sciences Center for Advanced Cardiovascular Technology, University of California, Irvine, CA, USA; Department of Biomedical Engineering, University of California, Irvine, CA, USA.
⁶ Hematology/Oncology, Department of Medicine, University of California, Irvine, CA, USA; Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN, USA; Southern California Institute for Research and Education, VA Medical Center, Long Beach, CA, USA. Electronic address: kalpnag@hs.uci.edu.

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.

Keywords: Breast cancer; Morphine; Opioid; Pain; β-Endorphin.

Publication types

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

MeSH terms

Animals
Biomarkers / blood
Breast Neoplasms / blood*
Breast Neoplasms / diagnosis*
Cancer Pain / blood*
Cancer Pain / diagnosis*
Cell Line, Tumor
Disease Progression*
Female
Humans
Mice
Mice, Transgenic
beta-Endorphin / blood*

Substances

Biomarkers
beta-Endorphin

Abstract

Publication types

MeSH terms

Substances

Grants and funding