Inflamm-aging of the stem cell niche: breast cancer as a paradigmatic example: breakdown of the multi-shell cytokine network fuels cancer in aged people

Bioessays. 2012 Jan;34(1):40-9. doi: 10.1002/bies.201100104. Epub 2011 Nov 16.

Abstract

Inflamm-aging is a relatively new terminology used to describe the age-related increase in the systemic pro-inflammatory status of humans. Here, we represent inflamm-aging as a breakdown in the multi-shell cytokine network, in which stem cells and stromal fibroblasts (referred to as the stem cell niche) become pro-inflammatory cytokine over-expressing cells due to the accumulation of DNA damage. Inflamm-aging self-propagates owing to the capability of pro-inflammatory cytokines to ignite the DNA-damage response in other cells surrounding DNA-damaged cells. Macrophages, the major cellular player in inflamm-aging, amplify the phenomenon, by broadcasting pro-inflammatory signals at both local and systemic levels. On the basis of this, we propose that inflamm-aging is a major contributor to the increase in cancer incidence and progression in aged people. Breast cancer will be presented as a paradigmatic example for this relationship.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aged
  • Aging*
  • Breast Neoplasms / immunology
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Breast Neoplasms / physiopathology
  • Cell Communication
  • Cell Transformation, Neoplastic*
  • Cytokines / immunology
  • Cytokines / metabolism*
  • DNA Damage
  • Disease Progression
  • Female
  • Fibroblasts / cytology
  • Fibroblasts / metabolism
  • Humans
  • Inflammation / immunology
  • Inflammation / metabolism*
  • Inflammation / pathology
  • Inflammation / physiopathology
  • Macrophages / cytology
  • Macrophages / metabolism
  • Signal Transduction*
  • Stem Cell Niche
  • Stem Cells / cytology
  • Stem Cells / metabolism*
  • Stromal Cells / cytology
  • Stromal Cells / metabolism

Substances

  • Cytokines