title: STATs profiling reveals predominantly-activated STAT3 in cholangiocarcinoma genesis and progression.
abstract: BACKGROUND
  We investigated the aberrant expression of the STAT family in humans and liver fluke (Opisthorchis viverrini, Ov)-induced hamster cholangiocarcinoma (CCA) tissues.
  
  
  METHODS
  The expression and phosphorylation of STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b and STAT6 in human hamster CCA tissues were immunohistochemistry-profiled. Localizations of STAT5 in macrophages and lipopolysaccharide (LPS)-induced macrophage-conditioned media mediated STAT3 activation in CCA cells were demonstrated.
  
  
  RESULTS
  The expressions of STAT 1-4 and 6 were detected in the cytoplasm of hyperplastic bile ducts and tumor cells, whereas STAT5a and STAT5b were observed in macrophages and connective tissues surrounding tumor, respectively. The expressions of STAT3 and STAT5b were significantly observed in tumors with a poorer histological differentiation. STAT3 expression was significantly associated with shorter survival of CCA patients and was predominately activated in CCA cell lines. In the CCA-hamsters, STATs expression was gradually increased along the carcinogenesis, especially at 30 days post-infection in which the inflammatory response was markedly observed, showing the correlation between the inflammation and STATs activation. Moreover, LPS-induced macrophage-conditioned media could mediate STAT3 activation in CCA cells.
  
  
  CONCLUSIONS
  STAT3 is the major STAT, which plays roles in the inflammation that contributes to CCA carcinogenesis and progression and may serve as a marker for a poor prognosis of CCA.
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand; Liver Fluke and Cholangiocarcinoma Research Center, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Hasaya
authors.initials: H
authors.lastname: Dokduang
authors.forename: Anchalee
authors.initials: A
authors.lastname: Techasen
authors.forename: Nisana
authors.initials: N
authors.lastname: Namwat
authors.forename: Narong
authors.initials: N
authors.lastname: Khuntikeo
authors.forename: Chawalit
authors.initials: C
authors.lastname: Pairojkul
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Murakami
authors.forename: Watcharin
authors.initials: W
authors.lastname: Loilome
authors.forename: Puangrat
authors.initials: P
authors.lastname: Yongvanit
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001650:Bile Duct Neoplasms / Q000378:metabolism* / Q000469:parasitology / Q000473:pathology; D001653:Bile Ducts, Intrahepatic; D014408:Biomarkers, Tumor / Q000378:metabolism; D015153:Blotting, Western; D018281:Cholangiocarcinoma / Q000378:metabolism* / Q000469:parasitology / Q000473:pathology; D006224:Cricetinae; D018450:Disease Progression; D005211:Fascioliasis / Q000150:complications; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010766:Phosphorylation; D050791:STAT Transcription Factors / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015996:Survival Rate; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D050791:STAT Transcription Factors; D050796:STAT3 Transcription Factor
keywords: Cholangiocarcinoma; Inflammation; Signal transducer and activator of transcription 3