Metastasis-associated protein S100A4 induces a network of inflammatory cytokines that activate stromal cells to acquire pro-tumorigenic properties

Cancer Lett. 2014 Mar 1;344(1):28-39. doi: 10.1016/j.canlet.2013.10.036. Epub 2013 Nov 8.

Abstract

Tumor cells have the ability to exploit stromal cells to facilitate metastasis. By using malignant melanoma as a model, we show that the stroma adjacent to metastatic lesions is enriched in the known metastasis-promoting protein S100A4. S100A4 stimulates cancer cells to secrete paracrine factors, such as inflammatory cytokines IL8, CCL2 and SAA, which activate stromal cells (endothelial cells and monocytes) so that they acquire tumor-supportive properties. Our data establishes S100A4 as an inducer of a cytokine network enabling tumor cells to engage angiogenic and inflammatory stromal cells, which might contribute to pro-metastatic activity of S100A4.

Keywords: Cytokines; Melanoma; Metastasis; S100A4; Tumor-stroma interactions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cytokines / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Heterografts
  • Humans
  • Immunohistochemistry
  • Inflammation / metabolism
  • Melanoma / metabolism*
  • Melanoma / pathology
  • Mice
  • Mice, Nude
  • Neoplasm Invasiveness
  • Real-Time Polymerase Chain Reaction
  • Receptor Cross-Talk / physiology
  • S100 Calcium-Binding Protein A4
  • S100 Proteins / metabolism*
  • Stromal Cells / metabolism*
  • Stromal Cells / pathology
  • Tumor Microenvironment / physiology*

Substances

  • Cytokines
  • S100 Calcium-Binding Protein A4
  • S100 Proteins
  • S100A4 protein, human