title: Human pancreatic cancer cells express non-functional Fas receptors and counterattack lymphocytes by expressing Fas ligand; a potential mechanism for immune escape.
abstract: The aim of this study was to investigate the expression and functional status of Fas ligand (FasL) and its receptor (Fas) in human pancreatic cancers. Using RT-PCR and Western blotting, Fas and FasL were expressed in seven surgically resected pancreatic cancer specimens and five cell lines; Capan-1, AsPC-1, BxPC-3, PANC-1, and MIA PaCa-2. In the resected specimens, pancreatic cancer cells induced apoptosis in the surrounding lymphoid cells. In coculture experiments of pancreatic cancer and Jurkat T cells, 50% of Jurkat T cells underwent apoptosis after 2 days, however, almost all pancreatic cancer cells remained viable. In addition, by testing Fas function using anti-Fas antibody (CH11), all cell lines were resistant to Fas-mediated apoptosis except Capan-1 cells which showed sensitivity similar to that of Jurkat T cells. These results suggest that pancreatic cancer cells evade immune surveillance by expression of FasL and non-functioning Fas that allow them to activated T-cells. These tumor escape mechanisms may contribute to the rapid fatal course of pancreatic cancer.
authors: Department of Surgery II, School of Medicine, Kanazawa University, Kanazawa 920-0934, Japan. aymann1@yahoo.com
authors: A
authors: A
authors: Elnemr
authors: T
authors: T
authors: Ohta
authors: A
authors: A
authors: Yachie
authors: M
authors: M
authors: Kayahara
authors: H
authors: H
authors: Kitagawa
authors: I
authors: I
authors: Ninomiya
authors: S
authors: S
authors: Fushida
authors: T
authors: T
authors: Fujimura
authors: G
authors: G
authors: Nishimura
authors: K
authors: K
authors: Shimizu
authors: K
authors: K
authors: Miwa
mesh_terms: D017209:Apoptosis; D015153:Blotting, Western; D002450:Cell Communication; D016923:Cell Death; D053222:Fas Ligand Protein; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D019169:Jurkat Cells; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D019139:Tumor Escape; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism*
chemical_list: C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D019014:fas Receptor