The wound healing, chronic fibrosis, and cancer progression triad

Physiol Genomics. 2014 Apr 1;46(7):223-44. doi: 10.1152/physiolgenomics.00158.2013. Epub 2014 Feb 11.


For decades tumors have been recognized as "wounds that do not heal." Besides the commonalities that tumors and wounded tissues share, the process of wound healing also portrays similar characteristics with chronic fibrosis. In this review, we suggest a tight interrelationship, which is governed as a concurrence of cellular and microenvironmental reactivity among wound healing, chronic fibrosis, and cancer development/progression (i.e., the WHFC triad). It is clear that the same cell types, as well as soluble and matrix elements that drive wound healing (including regeneration) via distinct signaling pathways, also fuel chronic fibrosis and tumor progression. Hence, here we review the relationship between fibrosis and cancer through the lens of wound healing.

Keywords: cancer; desmoplasia; epithelial-to-mesenchymal transition; fibrosis; myofibroblasts; regeneration; tumor stroma; tumor- or cancer-associated fibroblasts; wound healing.

Publication types

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

MeSH terms

  • Blood Coagulation
  • Chronic Disease
  • Disease Progression
  • Fibrosis*
  • Humans
  • Neoplasms / pathology*
  • Wound Healing*