Abstract
Abstract Despite the survival of breast cancer (BrCa) patients, there is still demand to better understand metastasis as the obvious mark for most aggressive breast cancers. Recent evidence highlighted the possible involvement of chemokines and their cognate receptors in BrCa progression and metastasis. Expression and functional role of CXCR6 and CXCL16 have been investigated in different types of cancer. ADAM10 is also known to regulate the metastatic process by the proteolytic shedding of CXCL16 creating a soluble form of CXCL16. High levels of soluble CXCL16 could support tumor progression by promoting migration and invasion of CXCR6 expressing BrCa cells. Here, we demonstrate the significance of CXCR6-CXCL16 axis in BrCa progression. In addition to increased CXCR6 expression, our tissue microarray analysis (TMA) showed increased expression of CXCL16 and ADAM10 in BrCa tissues. BrCa cell lines (MCF-7 and MBA-231) also showed higher expression of ADAM10 as compared to the normal epithelial cells (MCF-10A). Further, these BrCa cells showed increased migration and invasion towards CXCL16 gradient that is due to high expression of CXCR6 and ADAM10. Hence, our findings suggest the clinical and biological significance of ADAM10 and soluble CXCL16 in BrCa progression. We also highlight the potential of ADAM10 and soluble CXCL16 as prognostic markers and new therapeutic target for BrCa. Citation Format: Dominique N. Gales, Hina Mir, Neeraj Kapur, James W. Lillard, Shailesh Singh. ADAM10 promotes breast cancer via CXCL16 constitutive cleavage and CXCR6 signaling [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5080.
Published Version
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