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Tumor‐induced Factor (CXCL3) suppresses tumor initiation
Author(s) -
Cheung WingTai,
Li ZhouFang,
Jin Lili,
Wang DaKui,
Sun Meina,
Qi Wei,
Ma Qiang,
Zhang Li,
Chu Chun,
Liu Xing,
Lee Susanna S.T.,
Wise Helen,
To KaFai,
Shi Ying,
Zhou Naiming
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.lb532
Subject(s) - cancer research , biology , exon , carcinogenesis , microbiology and biotechnology , chemotaxis , angiogenesis , gene , receptor , genetics
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 phosphorylation. Functional studies showed that TIF induced blood vessel formation and chemotaxis of CXCR2‐expressing cells. Overexpression of TIF in CHO‐K1 cells indicated that secreted mature TIF functioned as an autocrine factor and promoted anchorage‐independent growth. Unexpectedly, xenograft studies suggested that TIF delayed the onset of tumor formation but without exerting any inhibitory effect on tumor growth. These results suggest TIF suppresses tumor initiation and could be therapeutically valuable for preventing cancer relapse. Support or Funding Information The project was partially funded by a CUHK Direct grant (2041596) and a research grant from HKSAR Health and Medical Research Fund (HMRF 02133116) to WTC, and also supported by grants from the Ministry of Science and Technology of China (2012CB910402 and 2012AA020303), and the National Natural Science Foundation of China (81173106) to NMZ.