Role of E-cadherin in peritoneal dissemination of the pancreatic cancer cell line, Panc-1, through regulation of cell to cell contact

The present study was designed to clarify the molecules responsible for peritoneal dissemination of cancer cells. We established sublines with high (HP cells) and low (LP cells) passing activity through the membrane of a transwell chamber. The cell lines were established from the human pancreatic cancer cell line, Panc-1. LP cells demonstrated an octagonal shape and tight adhesion, whereas HP cells exhibited a spindle shape and grew with less cell-cell contact in vitro. It was found that HP cells demonstrated a high degree of peritoneal dissemination in nude mice following peritoneal injection of these cells compared to LP cells. We subsequently investigated the expression of certain adhesion molecules. Consequently, we found that LP cells exhibited a stronger expression of E-cadherin than HP cells. On the other hand, there was no difference in the expression of CD44H and pi integrin between these two sublines. Passing activity of LP cells through the membrane of the invasion chamber increased to nearly equal levels with HP cells following treatment with anti-human E-cadherin antibody. Moreover, transfection of mouse E-cadherin cDNA into HP cells reduced both passing activity through the membrane of the invasion chamber and peritoneal dissemination in nude mice to levels similar to that of LP cells. In conclusion, these results indicated that loss of E-cadherin facilitates both passing activity in an invasion chamber and peritoneal dissemination, playing a causative role in peritoneal dissemination of cancer cells. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.