The CXCL7/CXCR2 axis and the migration of breast cells toward the malignant phenotype.

Abstract

181 Background: A component of the epithelial to mesenchymal transition (EMT) is degradation of extracellular matrix and acquisition of migration, both of which support invasiveness. The expression of CXCL7 is associated with the invasive phenotype through interaction with the CXCL7/CXCR2 axis and heparan sulfate. The purpose of this study is to quantify the expression of genes associated with EMT by CXCL7-expressing cells with the migration/invasive phenotype. Methods: Total RNA from CXCL7-transfected breast cells (MCF10AT) was tested for relative gene expression using RT2 Profiler PCR array for EMT (SABiosciences). Vector transfected cells were compared. Each result was verified by real time PCR assay. In parallel, migration assays were performed quantitatively using transwell membranes and qualitatively with the scratch test and photodocumented. Results: The expression of GNG11 and TCF4 was upregulated and SPP1 downregulated as expected for the EMT profile. Specifically, GNG11 (Guanine nucleotide binding protein (G protein), gamma 11) expression was increased 2.94 fold and TCF4 (Transcription factor 4) increased 1.89 fold. The expression of SPP1 (Secreted phosphoprotein 1) was decreased by 6.8 fold. The expression of ZEB2 (Zinc finger E-box binding homeobox 2) was decreased by 1.96 as a transcription factor. Migration of CXCL7-transfectants was significantly increased over vector controls and comparable to invasive isogenic breast cancer cells. Conclusions: The CXCL7-transfected cells with invasive phenotype express genes associated with the EMT expression profile including G-protein signaling pathway.