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J Pathol. 2019 Jul;248(3):377-389. doi: 10.1002/path.5267. Epub 2019 Apr 11.

IL-8 and CXCR1 expression is associated with cancer stem cell-like properties of clear cell renal cancer.

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Department of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland.
Life Science Zurich Graduate School, ETH and University of Zurich, Zurich, Switzerland.
Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.
Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Clinic of Internal Medicine I, Faculty of Medicine, Medical Center - University of Freiburg, Freiburg im Breisgau, Germany.


Recent studies suggest that clear cell renal cell carcinoma (ccRCC) possesses a rare population of cancer stem cells (CSCs) that might contribute to tumor heterogeneity, metastasis and therapeutic resistance. Nevertheless, their relevance for renal cancer is still unclear. In this study, we successfully isolated CSCs from established human ccRCC cell lines. CSCs displayed high expression of the chemokine IL-8 and its receptor CXCR1. While recombinant IL-8 significantly increased CSC number and properties in vitro, CXCR1 inhibition using an anti-CXCR1 antibody or repertaxin significantly reduced these features. After injection into immune-deficient mice, CSCs formed primary tumors that metastasized to the lung and liver. All xenografted tumors in mice expressed high levels of IL-8 and CXCR1. Furthermore, IL-8/CXCR1 expression significantly correlated with decreased overall survival in ccRCC patients. These results suggest that the IL-8/CXCR1 phenotype is associated with CSC-like properties in renal cancer. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.


CXCL8; CXCR1; IL-8; metastasis; renal cancer; stem cells; xenografts

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