SDF-1alpha concentration dependent modulation of RhoA and Rac1 modifies breast cancer and stromal cells interaction

BMC Cancer. 2015 Aug 1:15:569. doi: 10.1186/s12885-015-1556-7.

Abstract

Background: The interaction of SDF-1alpha with its receptor CXCR4 plays a role in the occurrence of distant metastasis in many solid tumors. This interaction increases migration from primary sites as well as homing at distant sites.

Methods: Here we investigated how SDF-1α could modulate both migration and adhesion of cancer cells through the modulation of RhoGTPases.

Results: We show that different concentrations of SDF-1α modulate the balance of adhesion and migration in cancer cells. Increased migration was obtained at 50 and 100 ng/ml of SDF-1α; however migration was reduced at 200 ng/ml. The adhesion between breast cancer cells and BMHC was significantly increased by SDF-1α treatment at 200 ng/ml and reduced using a blocking monoclonal antibody against CXCR4. We showed that at low SDF-1α concentration, RhoA was activated and overexpressed, while at high concentration Rac1 was promoting SDF-1α mediating-cell adhesion.

Conclusion: We conclude that SDF-1α concentration modulates migration and adhesion of breast cancer cells, by controlling expression and activation of RhoGTPases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / metabolism*
  • Cell Adhesion
  • Cell Line, Tumor
  • Cell Movement
  • Chemokine CXCL12 / metabolism
  • Chemokine CXCL12 / pharmacology*
  • Coculture Techniques
  • Female
  • Humans
  • MCF-7 Cells
  • Stromal Cells / cytology
  • Stromal Cells / physiology*
  • rac1 GTP-Binding Protein / metabolism*
  • rhoA GTP-Binding Protein / metabolism*

Substances

  • CXCL12 protein, human
  • Chemokine CXCL12
  • RAC1 protein, human
  • RHOA protein, human
  • rac1 GTP-Binding Protein
  • rhoA GTP-Binding Protein