Tumor-induced Factor (CXCL3) suppresses tumor initiation

Previously our lab uncovered a putative chemokine tumor-induced factor (TIF) from a mouse xenograft model of copy number variation (CNV)-mediated G protein-coupled receptor (GPCR) MAS-driven tumorigenesis. Sequence analysis and chemotactic study suggested that TIF was likely to be a hamster homolog of human GROγ (CXCL3) [IJC 125 (2009): 1316–1327]. Subsequently, genomic study of CHO-K1 cells indicated that Tif gene consisted of 4 exons, characterized with an antisense B1 element which is embedded in the fourth exon (GenBank Accession No: EU293869). Two Tif transcripts were identified which shared identical sequences except that a string of 71-nt derived from the antisense B1 element was deficient in the shorter transcript. By using the 71-nt sequence as a probe, B1-like RNA ladder was detected in xenografts. Pharmacological studies suggested that TIF activated Gi-coupled CXCR2 and suppressed forskolin-stimulated cAMP accumulation. In addition, TIF also induced calcium mobilization and ERK1/2 phosphorylati...