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- W3033133076 abstract "5334 Metastasis is responsible for all breast cancer (BrCa)- related deaths; therefore, therapies designed to prevent the spread of BrCa cells are greatly needed. The reasons why breast carcinomas preferentially metastasize to lymph nodes, bone, brain and lung are not fully understood. Similarly, the anti-apoptotic mechanisms employed by BrCa cells to survive in serum-free environments and apoptosis-inducing therapeutics are numerous and contribute significantly to the morbidity and mortality of this disease. Chemokines have been demonstrated to support BrCa metastasis and may also activate anti-apoptotic mechanisms. In this regard, BrCa cells express functionally active CXCR3, CXCR4 and CXCR7 to presumably support adhesion, invasion, and cell survival. The ligands for CXCR7 are CXCL11 (which also binds CXCR3) and CXCL12 (which also binds CXCR4); calcitonin-gene related peptide (CGRP) and adrenomedullin (AM) have also been suggested as potential CXCR7 ligands, which is somewhat controversial since these bioactive peptides have been definitively shown to bind class B G-protein coupled receptors (GPCRs) and not chemokine receptors (class A GPCRs). Nevertheless, these ligands are expressed by activated stroma as well as vascular and lymphatic endothelial cells, which might support motility, adherence and survival of BrCa cells. Indeed, all of these potential CXCR7 ligands are elevated in tissue and serum from patients with a variety of systemic diseases, including BrCa. We provide evidence that breast cancer cell lines express CXCR7 and its expression correlates with disease stage. We also confirm that this receptor; along with CXCR3 and CXCR4, are expressed by BrCa cell lines. We further show that CXCR7 is responsive to CXCL11, CXCL12, and adrenomedullin, but not CGRP. Lastly, for the first time to our knowledge, we demonstrate that CXCL11 and AM lead to rapid CXCR3 desensitization on BrCa cells, while CXCL11, CXCL12, and AM differentially modulates CXCR7 clustering on BrCa cell lines. Taken together, these studies provide important and novel information regarding the cellular and molecular mechanisms involved in CXCR3- and CXCR7-mediated breast cancer metastasis." @default.
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- W3033133076 date "2008-05-01" @default.
- W3033133076 modified "2023-09-27" @default.
- W3033133076 title "CXCR7 and CXCR3 interactions promote breast cancer (BrCa) cell migration, adhesion and survival" @default.
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