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

Jennifer Pasquier, Nadine Abu-Kaoud, Houari Abdesselem, Aisha Madani, Jessica Hoarau, Hamda Al Thawadi, Fabien Vidal, Bettina Couderc, Gilles Favre, Arash Rafii Tabrizi

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10 Citations (Scopus)

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

Original languageEnglish
Article number569
JournalBMC Cancer
Volume15
Issue number1
DOIs
Publication statusPublished - 1 Aug 2015

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Keywords

  • Breast cancer
  • Metastasis
  • SDF-1alpha
  • Stromal cells
  • Tumor microenvironment

ASJC Scopus subject areas

  • Oncology
  • Genetics
  • Cancer Research

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