Social isolation stress facilitates chemically induced oral carcinogenesis

PLoS One. 2021 Jan 7;16(1):e0245190. doi: 10.1371/journal.pone.0245190. eCollection 2021.

Abstract

Social isolation has affected a large number of people and may lead to impairment of physical and mental health. Although stress resulting from social isolation may increase cancer progression, its interference on tumorigenesis is poorly known. In this study, we used a preclinical model to evaluate the effects of social isolation stress on chemically induced oral carcinogenesis. Sixty-two 21-day-old male Wistar rats were divided into isolated and grouped groups. After 90 days of age, the rats from both groups underwent oral carcinogenesis with 4-nitroquinoline 1-oxide (4NQO) for 20 weeks. All rats were assessed for depressive-like behavior and euthanized for oral squamous cell carcinoma (OSCC) diagnosis and measurement of inflammatory mediators in the tumor microenvironment. Social isolation stress increased the OSCC occurrence by 20.4% when compared to control. Isolated rats also showed higher tumor volume and cachexia than the grouped rats. Social isolation did not induce changes in the depressive-like behavior after carcinogenic induction. Tumors from stressed rats had increased levels of the inflammatory mediators, TNF-alpha, IL1-beta and MCP-1. The concentrations of TNF-alpha and MCP-1 were significantly increased in the large tumors from isolated animals. Higher tumor levels of TNF-alpha, IL-6, IL1-beta and MCP-1 were positively correlated with OSCC growth. This study provides the first evidence that social isolation stress may facilitate OSCC occurrence and tumor progression, an event accompanied by increased local levels of inflammatory mediators.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Nitroquinoline-1-oxide / toxicity*
  • Animals
  • Behavior, Animal*
  • Cytokines / metabolism
  • Depression* / metabolism
  • Depression* / pathology
  • Depression* / physiopathology
  • Head and Neck Neoplasms* / chemically induced
  • Head and Neck Neoplasms* / metabolism
  • Head and Neck Neoplasms* / pathology
  • Head and Neck Neoplasms* / physiopathology
  • Inflammation Mediators / metabolism
  • Male
  • Neoplasm Proteins / metabolism
  • Rats
  • Rats, Wistar
  • Social Isolation*
  • Squamous Cell Carcinoma of Head and Neck* / chemically induced
  • Squamous Cell Carcinoma of Head and Neck* / metabolism
  • Squamous Cell Carcinoma of Head and Neck* / pathology
  • Squamous Cell Carcinoma of Head and Neck* / physiopathology
  • Stress, Psychological* / metabolism
  • Stress, Psychological* / pathology
  • Stress, Psychological* / physiopathology

Substances

  • Cytokines
  • Inflammation Mediators
  • Neoplasm Proteins
  • 4-Nitroquinoline-1-oxide

Grants and funding

This study was supported by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES; https://capes.gov.br/) and São Paulo State Research Foundation (FAPESP; http://www.fapesp.br/). CAPES Grant 001 supported FAV in her master-degree research. FAPESP Grant 2016/25255-0 designated to DGB supported Psychosomatic Research Center's studies. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.