Recent advances reveal IL-8 signaling as a potential key to targeting breast cancer stem cells.
Affiliation
Breast Biology, Institute of Cancer Sciences, University of Manchester, Paterson Building, Wilmslow Road, Manchester, M20 4BX, UK. robert.clarke@manchester.ac.uk.Issue Date
2013-08-30
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Show full item recordAbstract
Breast cancer stem-like cells (CSCs) are an important therapeutic target as they are purported to be responsible for tumor initiation, maintenance, metastases, and disease recurrence. Interleukin-8 (IL-8) is upregulated in breast cancer compared with normal breast tissue and is associated with poor prognosis. IL-8 is reported to promote breast cancer progression by increasing cell invasion, angiogenesis, and metastases and is upregulated in HER2-positive cancers. Recently, we and others have established that IL-8 via its cognate receptors, CXCR1 and CXCR2, is also involved in regulating breast CSC activity. Our work demonstrates that in metastatic breast CSCs, CXCR1/2 signals via transactivation of HER2. Given the importance of HER2 in breast cancer and in regulating CSC activity, a pathway driving the activation of these receptors would have important biological and clinical consequences, especially in tumors that express high levels of IL-8 and other CXCR1/2-activating ligands. Here, we review the IL-8 signaling pathway and the role of HER2 in maintaining an IL-8 inflammatory loop and discuss the potential of combining CXCR1/2 inhibitors with other treatments such as HER2-targeted therapy as a novel approach to eliminate CSCs and improve patient survival.Citation
Recent advances reveal IL-8 signaling as a potential key to targeting breast cancer stem cells. 2013, 15 (4):210 Breast Cancer Res.Journal
Breast Cancer ResearchDOI
10.1186/bcr3436PubMed ID
24041156Type
ArticleLanguage
enISSN
1465-542Xae974a485f413a2113503eed53cd6c53
10.1186/bcr3436
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