SDF-1α mediates wound-promoted tumor growth in a syngeneic orthotopic mouse model of breast cancer

PLoS One. 2013 Apr 11;8(4):e60919. doi: 10.1371/journal.pone.0060919. Print 2013.

Abstract

Increased growth of residual tumors in the proximity of acute surgical wounds has been reported; however, the mechanisms of wound-promoted tumor growth remain unknown. Here, we used a syngeneic, orthotopic mouse model of breast cancer to study mechanisms of wound-promoted tumor growth. Our results demonstrate that exposure of metastatic mouse breast cancer cells (4T1) to SDF-1α, which is increased in wound fluid, results in increased tumor growth. Both, wounding and exposure of 4T1 cells to SDF-1α not only increased tumor growth, but also tumor cell proliferation rate and stromal collagen deposition. Conversely, systemic inhibition of SDF-1α signaling with the small molecule AMD 3100 abolished the effect of wounding, and decreased cell proliferation, collagen deposition, and neoangiogenesis to the levels observed in control animals. Furthermore, using different mouse strains we could demonstrate that the effect of wounding on tumor growth and SDF-1α levels is host dependent and varies between mouse strains. Our results show that wound-promoted tumor growth is mediated by elevated SDF-1α levels and indicate that the effect of acute wounds on tumor growth depends on the predetermined wound response of the host background and its predetermined wound response.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Analysis of Variance
  • Animals
  • Azo Compounds
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / etiology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Chemokine CXCL12 / pharmacology*
  • Collagen / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Heterocyclic Compounds
  • Immunohistochemistry
  • Mice
  • Mice, Inbred BALB C
  • Microarray Analysis
  • Signal Transduction / drug effects
  • Statistics, Nonparametric
  • Wounds and Injuries / complications*

Substances

  • Azo Compounds
  • Chemokine CXCL12
  • Heterocyclic Compounds
  • C.I. direct red 80
  • Collagen
  • plerixafor