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Luminal B Breast Cancer Progression : CXCR4/CXCL12 Signaling and Protumor Macrophages

Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,[email protected], https://plus.google.com/communities/1... , ,https://plus.google.com/u/0/+Alexandr... , / @otolaryngologistorlent-med3259 , / @alexandrosg.sfakianakis4746 , https://twitter.com/g_orl?lang=el, / alexandrossfakianakis , CXCR4/CXCL12 Signaling and Protumor Macrophages in Primary Tumors and Sentinel Lymph Nodes Are Involved in Luminal B Breast Cancer Progression via Disease Markers Luminal B breast cancers (BC) have a more aggressive behavior associated with a higher rate of tumor relapse and worse prognosis compared to luminal A tumors. In this study, we evaluated the involvement of specific epithelial-to-mesenchymal transition- (EMT-) and immune-related pathways in the dissemination of luminal B BC cells. The expression of 42 EMT- and immune-related genes was evaluated in matched sentinel lymph nodes (SLNs) analyzed by the one-step nucleic acid amplification assay (OSNA) and primary tumors of 40 luminal B BC patients by gene array and immunohistochemistry. The results were validated in an independent group of 150 luminal B tumors by immunohistochemistry and immunofluorescence and using gene expression data from 315 luminal B BC patients included in the Metabric dataset. We found that the expression of CXCR4 () and CD163 () was significantly upregulated in SLNs of recurrent luminal B BC patients. Luminal B primary tumors overexpressing CXCR4 were characterized by an increased expression of vimentin and a high content of CD163-positive macrophages. Bioinformatics analysis confirmed the correlation of CXCR4 with CXCL12, VIM, and CD163 expression and LN involvement. Our results suggest that the upregulation of the CXCR4/CXCL12 pathway and the presence of protumor macrophages in the primary tumor and SLNs sustain the aggressiveness of an important subgroup of luminal B BC. Add tags (Currently: A, Medicine by Alexandros G. Sfakianakis)

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