Molecular and functional characterization of tumor-induced factor (TIF): Hamster homolog of CXCL3 (GROγ) displays tumor suppressive activity. (February 2018)

• Record Type: Journal Article
• Authors: Jin, Lili; Li, Zhou-Fang; Wang, Da-Kui; Sun, Meina; Qi, Wei; Ma, Qiang; Zhang, Li; Chu, Chun; Chan, Elaine Y.M.; Lee, Susanna S.T.; Wise, Helen; To, Ka-Fai; Shi, Ying; Zhou, Naiming; Cheung, Wing-Tai
• Is Part Of: Cytokine. Volume 102(2018)
• Page Start: 62
• Page End: 75
• Publication Date: 2018-02
• Subjects: CXCL1 -- CXCL3 -- CXCR2 -- GRO -- IL-8 -- MAS -- Tumor-induced factor; Chemokine; Ab antibody -- CHO-K1 Chinese hamster ovary-K1 -- CNV copy number variation -- CXCR2 CXC chemokine receptor 2 -- CRE cAMP-response elements -- DCIP1 dendritic cell inflammatory protein 1 -- DIG digoxigenin -- CINC2 cytokine-induced neutrophil chemoattractant 2 -- DMEM Dulbecco's modified Eagles's medium -- ELISA enzyme-linked immunosorbent assay -- EGFP enhanced green fluorescent protein -- ELR glutamate-leucine-arginine -- EGTA ethylene glycol-bis(β-aminoethyl ether)-N, N, N′, N′-tetraacetic acid -- ERK1/2 extracellular signal-regulated kinase 1/2 -- F-actin filamentous actin -- FBS fetal bovine serum -- FITC fluorescein isothiocyanate -- FSK forskolin -- GFP green fluorescent protein -- GPCR G protein-coupled receptor -- GRO growth regulated -- HEK293T human embryonic kidney 293T cell -- HEPES 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid -- Ig immunoglobulins -- IL interleukin -- MTT 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium -- MEF mouse embryonic fibroblasts -- nt nucleotide -- ORF open reading frame -- PAGE polyacrylamide gel electrophoresis -- PBS phosphate-buffered saline -- PCR polymerase chain reaction -- PMA 12-O-tetradecanoylphorbol-13-acetate -- PKA protein kinase A -- PTX pertussis toxin -- RACE rapid amplification of 5′-cDNA end -- RIPA radioimmunoprecipitation assay -- TBST Tris-buffered saline and Tween 20 -- TIF tumor-induced factor -- UTR untranslated region; Cytokines -- Periodicals; 571.844
• DOI: 10.1016/j.cyto.2017.12.019
• Languages: English
• ISSNs: 1043-4666

Abstract

Highlights: TIF gene consisted of 4 exons and embedded an antisense B1 element. TIF induced chemotaxis and neovessel formation. TIF triggered Gi-depending signaling pathways upon activation CXCR2. TIF promoted anchorage-independent growth of CHO but suppressed MEF proliferation. TIF delayed the onset of tumor formation but exerted no effect on tumor growth. Abstract: Previously our lab has created a mouse ovarian xenograft model of copy number variation (CNV)-mediated G protein-coupled receptor (GPCR) MAS-driven tumorigenesis, and RNA profiling identified a putative chemokine tumor-induced factor ( Tif ). Sequence analysis and chemotactic study suggested that Tif was likely to be a hamster homolog of human GROγ ( CXCL3 ) [IJC 125 (2009): 1316–1327]. In the present study, we report the molecular and functional characterization of the Tif gene. 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. 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. Of interests, B1- like RNA ladder was detected in xenografts. Functional studies showed that TIF induced chemotaxis and neovessel formation. Pharmacological studies suggested that TIF activated Gi-coupled CXCR2 and induced both calcium mobilization and ERK1/2 phosphorylation, and suppressed forskolin-stimulated cAMP accumulation. In addition, secreted matured TIF functioned as an autocrine factor and promoted anchorage-independent growth. Unexpectedly, TIF delayed the onset of tumor formation, possibly via suppressing proliferation of stromal fibroblasts. However, TIF did not exert any inhibitory effect on tumor growth. Potentially, TIF could be used for preventing cancer relapse.