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

ABSTRACT: 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.

SUBMITTER: Corro C

PROVIDER: S-EPMC6618115 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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

Corrò Claudia C Healy Marc E ME Engler Stefanie S Bodenmiller Bernd B Li Zhe Z Schraml Peter P Weber Achim A Frew Ian J IJ Rechsteiner Markus M Moch Holger H

The Journal of pathology 20190411 3

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 p ...[more]

PMID: 30883740

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Project description:Background:To elucidate the correlations between tumor microenvironment and clinical characteristics as well as prognosis in clear cell renal cell cancer (ccRCC) and investigate the immune-associated genes by a comprehensive analysis of The Cancer Genome Atlas (TCGA) database. Methods:We collected mRNA expression profiles of 537 ccRCC samples from the TCGA database. Immune scores and stromal scores were calculated by applying the ESTIMATE algorithm. We evaluated the correlation between immune/stromal scores and clinical characteristics as well as prognosis. The differentially expressed genes (DEGs) were screened between high immune/stromal score and low immune/stromal score groups by the cutoff of |log (fold change)|?>?1, P value <0.05 by using package "limma" in R. Functional enrichment analysis was performed by DAVID, and the protein-protein interaction network of intersected DEGs between stromal score and immune score groups was conducted using the STRING database. The Kaplan-Meier method was used to explore DEGs with predictive values in overall survival, and the prognostic DEGs were further validated in a Gene Expression Omnibus (GEO) dataset GSE29609. Results:A higher immune score was associated with T3/4 (vs. T1/2, P < 0.001), N1 (vs. N0, P=0.05), M1 (vs. M0, P=0.004), G3/4 (vs. G1/2, P < 0.001), advanced AJCC stage (P < 0.001), and shorter overall survival (P=0.04). Intersected DEGs between immune and stromal score groups were 48 upregulated and 47 downregulated genes, with 43 DEGs associated with overall survival in ccRCC. After validation by a cohort of 39 ccRCC cases with detailed follow-up information from GSE29609, six immune-associated DEGs including CASP5, HSD11B1, VSIG4, HMGCS2, HSD11B2, and OGDHL were demonstrated to be predictive of prognosis in ccRCC. Conclusions:Our study elucidated tight associations between immune score and clinical characteristics as well as prognosis in ccRCC. Moreover, six DEGs were explored and validated to exert predictive values in overall survival of ccRCC.

Dataset Information

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

Publications

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

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