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

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.