Clinical significance of Wnt-induced secreted protein-1 (WISP-1/CCN4) in esophageal squamous cell carcinoma

Anticancer Res. 2011 Mar;31(3):991-7.

Abstract

Background/aim: 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.

Patients and 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.

Conclusion: 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.

MeSH terms

  • Aged
  • Aged, 80 and over
  • CCN Intercellular Signaling Proteins
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Cell Line, Tumor
  • Esophageal Neoplasms / genetics
  • Esophageal Neoplasms / metabolism*
  • Esophageal Neoplasms / pathology
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Male
  • Middle Aged
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Survival Analysis

Substances

  • CCN Intercellular Signaling Proteins
  • CCN4 protein, human
  • Intracellular Signaling Peptides and Proteins
  • Proto-Oncogene Proteins