How Signaling Molecules Regulate Tumor Microenvironment: Parallels to Wound Repair

Molecules. 2017 Oct 26;22(11):1818. doi: 10.3390/molecules22111818.

Abstract

It is now suggested that the inhibition of biological programs that are associated with the tumor microenvironment may be critical to the diagnostics, prevention and treatment of cancer. On the other hand, a suitable wound microenvironment would accelerate tissue repair and prevent extensive scar formation. In the present review paper, we define key signaling molecules (growth factors, cytokines, chemokines, and galectins) involved in the formation of the tumor microenvironment that decrease overall survival and increase drug resistance in cancer suffering patients. Additional attention will also be given to show whether targeted modulation of these regulators promote tissue regeneration and wound management. Whole-genome transcriptome profiling, in vitro and animal experiments revealed that interleukin 6, interleukin 8, chemokine (C-X-C motif) ligand 1, galectin-1, and selected proteins of the extracellular matrix (e.g., fibronectin) do have similar regulation during wound healing and tumor growth. Published data demonstrate remarkable similarities between the tumor and wound microenvironments. Therefore, tailor made manipulation of cancer stroma can have important therapeutic consequences. Moreover, better understanding of cancer cell-stroma interaction can help to improve wound healing by supporting granulation tissue formation and process of reepithelization of extensive and chronic wounds as well as prevention of hypertrophic scars and formation of keloids.

Keywords: cancer; cytokine; galectin; stem cell; tissue repair.

Publication types

  • Review

MeSH terms

  • Animals
  • Cellular Microenvironment
  • Cytokines / metabolism
  • Galectins / metabolism
  • Humans
  • Immune System / cytology
  • Immune System / immunology
  • Immune System / metabolism
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Keloid / metabolism
  • Keloid / pathology
  • Neoplasms / immunology
  • Neoplasms / metabolism*
  • Neoplasms / pathology*
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology
  • Signal Transduction*
  • Tumor Microenvironment*
  • Wound Healing
  • Wounds and Injuries / immunology
  • Wounds and Injuries / metabolism
  • Wounds and Injuries / pathology

Substances

  • Cytokines
  • Galectins
  • Intercellular Signaling Peptides and Proteins