Abstract
We have shown that the 16D10 antigen located on the mucin-like COOH-terminal domain of the feto-acinar pancreatic protein (FAPP) is expressed at the surface of human pancreatic tumor cell lines such as SOJ-6 cell line. Furthermore, an in vivo study indicates that targeting this cell-membrane glycopeptide by the use of the monoclonal antibody (mAb) 16D10 inhibits the growth of SOJ-6 xenografts in nude mice. To validate the potential use of the mAb16D10 in immune therapy, this study examined the expression of 16D10 antigens at the surface of human pancreatic adenocarcinomas versus control tissues. We examined the reactivity of mAb16D10 and mAb8H8 with pancreatic ductal adenocarcinomas (PDAC) compared with controls by using immunohistochemistry and confocal laser scanning microscopy. mAb8H8 does react with control or nontumoral human pancreatic tissues. mAb16D10 has a strong and specific reactivity with PDAC and does not react with other cancers of epithelia or normal tissues tested. Notable, mAb16D10 mostly recognizes membrane of tumoral cells. Furthermore, mAb8H8 and mAb16D10 recognized a protein of 110 to 120 kDa in homogenates of nontumoral and tumoral human pancreatic tissues, respectively. This size correlates with that of FAPP or with that of the normal counterpart of FAPP, the so-called bile salt-dependent lipase. The results suggest that mAb16D10 presents a unique specificity against PDAC; consequently, it could be effective in immune therapy of this cancer. Furthermore, mAb16D10 and mAb8H8 pair might be useful for diagnosis purpose in discriminating tumoral from nontumoral human pancreatic tissues.
Highlights
The bile salt-dependent lipase (BSDL; E.C. 3.1.1.13) is found in the pancreatic secretions of all species from fish to human [1]
No staining was found in nontumoral tissue with mAb16D10, whereas pancreatic ductal adenocarcinomas (PDAC) sections were all positive to mAb16D10 (Fig. 1)
No significant progress has been made against the cancer of the exocrine pancreas, chemotherapy associated with radiotherapy has some positive effect on the survival of patients [31]
Summary
The bile salt-dependent lipase (BSDL; E.C. 3.1.1.13) is found in the pancreatic secretions of all species from fish to human [1] This enzyme participates in the intestinal processing of cholesteryl esters (2 – 4). During its transport from the endoplasmic reticulum up to the trans-Golgi network, BSDL is associated with intracellular membranes by means of a complex that involves glycosphingolipids of rafts [5] and the 94-kDa glucose-related protein [6, 7]. This Grp 94 controls the late folding steps and the sorting of the active enzyme toward secretion [8]. Once released from intracellular membranes, BSDL enters into the secretion route until the duodenum where it accomplishes its physiologic role
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