title: Clinical significance of Wnt-induced secreted protein-1 (WISP-1/CCN4) in esophageal squamous cell carcinoma.
abstract: OBJECTIVE
  The expression of Wingless/int-1 (Wnt)-induced secreted protein-1 (WISP-1/CCN4), a member of the Cyr61-CTGF-Nov (CCN) family, has been examined in several types of cancer. However, the correlation between the WISP-1 expression and the clinical features of esophageal squamous cell carcinoma (ESCC) remain to be elucidated. This study aimed to clarify the expression of WISP-1 protein in patients with ESCC and also to examine the function of WISP-1 in esophageal cancer cells in vitro.
  
  
  METHODS
  One-hundred and ninety patients with thoracic esophageal carcinoma underwent transthoracic subtotal esophagectomy-between 2005 and 2009. All patients that had received previous therapy were excluded and 105 out of the 190 ESCC samples were analyzed immunohistochemically using WISP-1 antibody. The expression of WISP-1 mRNA in esophageal cancer cell lines was analyzed by RT-PCR. Growth assay and invasion assays were performed using WISP-1 transfected cells.
  
  
  RESULTS
  The immunohistochemical analysis showed that WISP-1-positive cases were closely associated with tumor size, tumor type, lymph node metastasis and poor prognosis. There were significantly more WISP-1-positive infiltrative type tumors than expanding type tumors. In the esophageal cancer cell lines examined, only TE8 expressed WISP-1 mRNA. The growth of WISP-1-transfected cells was significantly increased in comparison to the control cells, but no differences in the invasion activity were observed between the transfected cells and control cells.
  
  
  CONCLUSIONS
  The expression of WISP-1 may play an important role in the progression of ESCC. WISP-1 could therefore be a clinical marker for a poor prognosis in patients with ESCC and may also be a therapeutic target to control the progression of ESCC.
authors.affiliation: FACS, Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Kumamoto City, Kumamoto, 860-8556, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Nagai
authors.forename: Masayuki
authors.initials: M
authors.lastname: Watanabe
authors.forename: Shinji
authors.initials: S
authors.lastname: Ishikawa
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Karashima
authors.forename: Junji
authors.initials: J
authors.lastname: Kurashige
authors.forename: Shiro
authors.initials: S
authors.lastname: Iwagami
authors.forename: Masaaki
authors.initials: M
authors.lastname: Iwatsuki
authors.forename: Yoshihumi
authors.initials: Y
authors.lastname: Baba
authors.forename: Yu
authors.initials: Y
authors.lastname: Imamura
authors.forename: Naoko
authors.initials: N
authors.lastname: Hayashi
authors.forename: Hideo
authors.initials: H
authors.lastname: Baba
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D055511:CCN Intercellular Signaling Proteins; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D016019:Survival Analysis
chemical_list: D055511:CCN Intercellular Signaling Proteins; C116396:CCN4 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D011518:Proto-Oncogene Proteins