20. Centralisation of pancreatic cancer surgery in Ireland

Abstract

Background: Pancreatic cancer still remains one of the most lethal diseases among all malignancies. One of the major reasons of this lethality is its invasive and metastatic behavior. Nevertheless, little is known about the molecular mechanisms regulating cell migration in pancreatic cancer cells. CD44 is a family of adhesion molecules and is implicated in the diverse physiological process including cell migration, growth, survival and differentiation. The purpose of this study is to investigate the clinical value of CD44 expression in pancreatic cancer tissues and reveal the detailed roles of this molecule in cancer cells. Materials and methods:We examined the CD44 expression pattern in resected cancer tissues obtained from patients with pancreatic cancer by immunohistochemistry. We investigated the expression of CD44 isoforms in pancreatic cancer using RT-PCR and the influence of inhibition of CD44 in a pancreatic cancer cell line using siRNA. Results:CD44 standard isoform, but not variant isoforms, wasmainly expressed in the lateral membrane of cancer cells. In 87 patients, 68 patients (78.2 %) showed strong CD44 expression in cancer cells, while 19 patients (21.8%) showed weak expression. Patients of strong CD44 expression group showed significantly better prognosis in disease free (p1⁄40.034) as well as overall survival (p1⁄40.002) compared with those in weak CD44 expression group. AsPC-1 cells treated with CD44 siRNA showed significantly more rapid cell migration ability than cells treated with negative control siRNA (p1⁄40.04). Cells inhibited CD44 expression by siRNA showed flat sheet like actin structure forming lamillipodia at the leading edge of the cell, whereas no such structure was seen in cells treated with negative control siRNA. Conclusions: These data suggest that CD44s expression in pancreatic cancer cells inhibits cell migration by the interference with lamillipodia formation, leading to favorable prognosis of the patient. Regulation of CD44 splicing may lead to the discovery of new therapeutic approaches for pancreatic cancer.