title: Inhibition of proliferation and migration of luminal and claudin-low breast cancer cells by PDGFR inhibitors.
abstract: BACKGROUND
  Platelet-derived growth factors (PDGFs) bind to two receptors, PDGFRα and PDGFRβ to mediate cell proliferation, migration and survival. Although epithelial cells typically do not express high levels of PDGFRs, their expression has been reported to increase in breast cancer cells that have undergone epithelial to mesenchymal transition.
  
  
  METHODS
  PDGFR signaling was inhibited using Sunitinib malate, Imatinib mesylate or Regorafenib in murine and human luminal-like and claudin-low mammary tumor cell lines or Masitinib in only the human cell lines. A scratch wound assay was used to assess tumor cell migration while immunofluorescence for phosphorylated histone H3 or cleaved caspase 3 was used to determine tumor cell proliferation and apoptosis, respectively.
  
  
  RESULTS
  Sunitinib and Regorafenib, but not Imatinib, were capable of significantly inhibiting the migration of both murine and human luminal-like and claudin-low breast cancer cells while Masitinib inhibited migration in both human breast cancer cell lines. Sunitinib but not Regorafenib or Imatinib also significantly suppressed tumor cell proliferation in all four cell lines tested while Masitinib had no significant effect on human breast cancer cell proliferation. None of the PDGFR inhibitors consistently regulated mammary tumor cell apoptosis.
  
  
  CONCLUSIONS
  Sunitinib, Regorafenib and Masitinib may prove clinically useful in inhibiting breast cancer cell migration and metastasis while only Sunitinib (and possibly Regorafenib in some breast cancer subtypes) is effective at inhibiting both migration and proliferation of breast cancer cells.
authors.affiliation: Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, ON N1G2W1 Canada.
authors.forename: Leanne
authors.initials: L
authors.lastname: Stalker
authors.affiliation: Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, ON N1G2W1 Canada.
authors.forename: James
authors.initials: J
authors.lastname: Pemberton
authors.affiliation: Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, ON N1G2W1 Canada ; Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, 50 Stone Road East, Guelph, ON N5A7Z1 Canada.
authors.forename: Roger A
authors.initials: RA
authors.lastname: Moorehead