Recent studies suggests 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. Further, 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.
The Journal of pathology. 2019 Mar 18 [Epub ahead of print]
Claudia Corrò, Marc Eammonn Healy, Stefanie Engler, Bernd Bodenmiller, Zhe Li, Peter Schraml, Achim Weber, Ian J Frew, Markus Rechsteiner, Holger Moch
Department of Pathology and Molecular Pathology, University Hospital Zurich, Switzerland., Institute of Molecular Life Sciences, University of Zurich, Switzerland., Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA., Clinic of Internal Medicine I, Faculty of Medicine, Medical Center - University of Freiburg, Germany.