The inflammatory network: bridging senescent stroma and epithelial tumorigenesis

Front Biosci (Landmark Ed). 2009 Jan 1;14(11):4044-57. doi: 10.2741/3511.

Abstract

Cellular senescence or aging, defined by permanent cell cycle arrest, is well known for its evolutionary advantage in protecting the organism from developing cancer; however, it is also acknowledged that aged stromal cells can significantly expedite epithelial tumorigenesis, although exactly how they function to augment tumor formation remains elusive. Recent evidence suggests that this tumor-promoting effect is likely mediated by diffusible pro-inflammatory molecules synthesized and released by senescent stromal fibroblasts, acting in a paracrine fashion on adjacent tumor epithelium. Mobilization of the inflammatory network by senescent fibroblasts has bifurcated roles on the epithelial and stromal compartments, converging on the promotion of epithelial tumorigenesis. A thorough understanding of the regulatory mechanisms underlying these events may lead to improved approaches in cancer treatment.

Publication types

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

MeSH terms

  • Cell Transformation, Neoplastic*
  • Cellular Senescence
  • Epithelial Cells / pathology*
  • Humans
  • Inflammation / pathology*
  • Neoplasms, Glandular and Epithelial / pathology*
  • Stromal Cells / pathology*