GSE183976
RNAseq transcriptome analysis of THP-1 macrophages activated by VHL-deficient kidney tubule cells
Clear-cell renal cell carcinoma (ccRCC) is the most prevalent subtype of renal cell carcinoma (up-to 70% of all RCC types). There is a very close causal correlation between ccRCC and inactivation of the tumor suppressor gene von Hippel-Lindau (VHL) located on chromosome 3p25-26. Up to 80% of sporadic ccRCC carry genomic mutations or epigenetic inactivation of VHL and nearly 100% familial ccRCC (in VHL disease) contain VHL deficiency. Accumulating evidence has indicated that ccRCC arises at the site of chronic inflammation and this solid tumor contains a substantial number of infiltrated immune cells. This indicates that ccRCC may be induced by the interaction between kidney tubule cells carrying inactivated VHL gene and the inflammatory microenvironment. In this study we characterized the interaction between VHL-deficient kidney tubule cells and macrophages with relevance to ccRCC formation, and found that human macrophages induced by VHL-deficient kidney tubule cells exhibit distinct gene expression program containing the signatures of tumor-associated macrophages that can promote ccRCC progression. Overall design: The partially differentiated macrophages derived from human monocyte precursor THP-1 cells [with 50 ng/ml phorbol 12-myristate-13-acetate (PMA)] were cocultured  in the Boyden chamber with human kidney tubule cell line HK-2 with (shVHL61) or without (shLuc) VHL knockdown. After 48 hr, total RNA was purified from macrophages and prepared sequencing.