Laminin γ2-chain fragment circulating level increases in patients with metastatic pancreatic ductal cell adenocarcinomas

Laminin-5 (LN5) is expressed solely by epithelial cells and considered to enhance cell migration after being cleaved by proteases, leading to the shedding of the N-terminal fragment of the LN5 γ2-chain (G2F). We estimated circulating G2F level in 181 patients with various digestive diseases and 15 healthy subjects. The G2F level in pancreatic ductal cell adenocarcinoma patients with liver metastases was markedly elevated, but that in patients without liver metastases was not significantly elevated. The G2F levels in patients with benign pancreatic tumours (pancreatic cysts and intraductal papillary mucinous tumours) were similar to that in healthy volunteers. On the other hand, the level of the γ1-chain is a common constituent of several laminin heterotrimers. The N-terminal fragment of γ1-chain (G1F) in the circulation of these patients was also determined, and a slight increase in G1F levels was observed only in hepatocellular carcinoma patients. Interestingly, a significant increase in circulating G2F/G1F ratio was observed in patients with bile duct and gallbladder carcinoma, as well as in those with metastatic pancreatic ductal cell adenocarcinoma. The increase in the circulating G2F level, particularly compared with circulating G1F level, should correlated with LN5 overexpression in invasive carcinomas, independently of basement membrane metabolism in the entire body.