Molecular and functional characterization of tumor-induced factor (TIF): Hamster homolog of CXCL3 (GROγ) displays tumor suppressive activity
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AbstractPreviously 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.
All Author(s) ListLili JIN, Zhou-Fang LI, Da-Kui WANG, Meina SUN, Wei QI, Qiang MA, Li ZHANG, Chun CHU, Elaine Y.M. CHAN, Susanna S.T. LEE, Helen WISE, Ka-Fai TO, Ying SHI, Naiming ZHOU, Wing-Tai CHEUNG
Journal nameCytokine
Volume Number102
Pages62 - 75
LanguagesEnglish-United Kingdom
KeywordsCXCL1, CXCL3, CXCR2, GRO, IL-8, MAS, Tumor-induced factor, Chemokine

Last updated on 2020-06-07 at 01:27