title: Retention of the fetoacinar pancreatic (FAP) protein to the endoplasmic reticulum of tumor cells.
abstract: The fetoacinar pancreatic (FAP) protein is a specific component of the human exocrine pancreas associated with the differentiation and proliferation of acinar cells. FAP expression is enhanced in cases of pancreatic exocrine cancer and it is found in relatively high concentrations in pathological pancreatic juices. However, tumor cell lines do not secrete FAP into the culture medium. In this paper we analyze the intracellular localization of FAP in cell lines and compare some biological properties of the tumoral FAP with the normal adult and fetal forms. Immunocytological experiments performed using Mab J28 which characterizes FAP, gave a staining pattern suggestive of FAP localization in the ER. Subcellular fractionation corroborated this localization and established that FAP is tightly associated with the microsomal membranes. The absence of reactivity of the tumoral FAP with wheat germ agglutinin lectin and its strong reactivity with concanavalin A is consistent with the idea that FAP in tumor cells does not reach the Golgi apparatus and it is consequently retained in the endoplasmic reticulum (ER). FAP contained in hepatic metastasis derived from pancreatic adenocarcinoma appeared to be similar, if not identical, to that expressed by cell lines. This supports the hypothesis that FAP retention in the ER of malignant cells is a physiological phenomenon and not the result of a modification of cell lines due to the culture conditions. FAP expressed by cancer cell lines and metastases appeared by sodium dodecyl sulfate polyacrylamide gel electrophoresis a homogeneous protein with a M(r) of 120,000. Instead, the secreted mature protein consists of a main component of M(r) 110,000 and shows pronounced polymorphism (dispersion from M(r) 110,000 to 80,000). Increased size of the ER-retained protein is likely due to elongation of the peptide chain. Defective processing in the ER as a result of amino acid mutation could therefore explain the behavior of this protein in tumors.
authors: Laboratoire d'Immunochimie, Institut de Recherches Scientifiques sur le Cancer, CNRS, Villejuif/France.
authors: F
authors: F
authors: Miralles
authors: F
authors: F
authors: Langa
authors: A
authors: A
authors: Mazo
authors: M J
authors: MJ
authors: Escribano
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism*; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000737:chemistry / Q000378:metabolism; D006023:Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008049:Lipase; D008861:Microsomes / Q000737:chemistry; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D006023:Glycoproteins; C054621:CEL protein, human; D008049:Lipase