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MECHANISMS MEDIATED BY CXCL 12 SIGNALING THROUGH CXCR4 AND CXCR7 IN BREAST CANCER LaSharon D. Mosley DECEMBER 2009 Interactions between chemokines and their receptors are involved in organspecific homing and propagation of metastatic breast cancer (BrCa) cells. BrCa cells express higher levels of CXCR4 and CXCR7 mRNA and cell surface protein, than normal human mammary epithelial cells (HMECs). CXCR4 is ubiquitously expressed by a multitude of cancerous and normal cell types; while CXCR7 is differentially expressed by T helper lymphocytes, cancer cells, and normal epithelium. Importantly, recent studies show CXCR7 is highly expressed by activated endothelial cells (Le., neovasculature), fetal liver cells, and many tumors, but not by non-transformed (or normal) human tissues. Unlike other chemokine receptors, activation of CXCR7 does not cause Ca+ mobilization/flux or cell migration. However, CXCR7 activation by its ligands (CXCL 12 or CXCL 11) provides signals for growth, survival, and adhesion. Preliminary studies demonstrated CXCR7 expression is significantly higher in BrCa cases than compared to non-neoplastic tissues. Further, CXCR7 mRNAs are elevated in the BrCa cell line MCF-7, with modest expression in MDA-MB-231 when

Mechanisms mediated by CXCL12 signaling through CXCR4 and CXCR7 in breast cancer.