Abstract
Pancreatic duct cell carcinoma (PDC) is one of the most malignant of the gastrointestinal tumors. Expression of the apoptosis-related factors Fas ligand (FasL) and caspase-3 and the antiapoptotic factor survivin was examined in PDC and in intraductal papillary-mucinous tumor (IPMT) by reverse transcriptase-polymerase chain reaction (RT-PCR), immunoblot analysis, and immunohistochemistry. Frequent expression of FasL was observed in PDC. The co-culture experiments showed that PANC-1 cells induced apoptosis of Jurkat cells, whereas the PANC-1 cells themselves and Jurkat cells cultured without the presence of PANC-1 showed few apoptotic changes. The immunoreactivity of caspase-3 was predominantly found in the cytoplasm of invasive tumors (PDC and invasive IPMT). There was a significant correlation between the cytoplasmic staining and malignant grade of the tumors. In contrast, the nuclear expression of this enzyme was significantly higher in noninvasive tumors than in invasive tumors. Survivin was more frequently expressed in malignant tumors than in benign tumors. In PDC, high levels of survivin expression were significantly associated with a reduction in the apoptotic index of the tumor cells. These findings suggest that: (1) Fas-L may play an important role in the ability of PDC to escape from immune surveillance through the induction of apoptosis in tumor-attacking lymphocytes; (2) cytoplasmic expression of caspase-3 may be related to the invasiveness of pancreatic tumors; and (3) the expression of survivin may be up-regulated during the development of cancer by reducing the cancer cell apoptosis.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Loftus EV Jr, Olivares-Pakzad BA, Batts KP, et al (1996) Intraductal papillary-mucinous tumors of the pancreas: clinicopathologic features, outcome, and nomenclature. Gastroenterology 110:1909–1918
Satoh K, Shimosegawa T, Moriizumi S, et al (1996) K-ras mutation and p53 protein accumulation in intraductal mucin-hypersecreting neoplasms of the pancreas. Pancreas 12:362–368
Satoh K, Sasano H, Shimosegawa T, et al (1993) An immunohistochemical study of the c-erb B-2 oncogene product in intraductal mucin-hypersecreting neoplasms and in ductal cell carcinomas of the pancreas. Cancer 72:51–56
Fukushige S, Furukawa T, Satoh K, et al (1998) Loss of chromosome 18q is an early event in pancreatic ductal tumorigenesis. Cancer Res 58:4222–4226
Sugiyama M, Atomi Y (1998) Intraductal papillary-mucionus tumors of the pancreas: imaging studies and treatment strategies. Ann Surg 228:685–691
Yasuda H, Takada T, Amano H, et al (1998) Surgery for mucin-producing pancreatic tumor. Hepatogastroenterology 45:2009–2015
Thompson CB (1995) Apoptosis in the pathogenesis and treatment of disease. Science 267:1456–1462
Nagata S, Golstein P (1995) The Fas death factor. Science 267:1449–1456
Yonehara S, Ishii A, Yonehara M (1989) A cell-killing monoclonal antibody (anti-Fas) to cell surface antigen co-downregulated with the receptor of tumor necrosis factor. J Exp Med 169:1747–1756
Oehn A, Behrman I, Falk W, et al (1992) Purification and molecular cloning of the APO-1 cell surface antigen, a member of the tumor necrosis factor/nerve growth factor receptor family: sequence identity with the Fas antigen. J Biol Chem 267:10709–10715
Singer GG, Abbas AK (1994) The Fas antigen is involved in peripheral but not thymic deletion of T lymphocytes in T cell receptor transgenic mice. Immunity 1:365–371
Alderson MR, Tough TW, Davis-Smith T, et al (1995) Fas ligand mediates activation-induced cell death in human T lymphocytes. J Exp Med 181:71–77
Hahne D, Rimoldi M, Schröter P, et al (1996) Melanoma cell expression of Fas (Apo-1/ CD95) ligand: implications for tumor immune escape. Science 274:1363–1366
Strand S, Hofmann WJ, Hug H, et al (1996) Lymphocyte apoptosis induced by CD95 (APO-1/Fas) ligand-expressing tumor cells: a mechanism of immune evasion? Nat Med 2:1361–1366
O’Connell BJ, O’Sullivan GC, Collins JK, et al (1996) The Fas counterattack: Fas-mediated T cell killing by colon cancer cells expressing Fas ligand. J Exp Med 184:1075–1082
Shiraki K, Tsuji N, Shioda T, et al (1997) Expression of Fas ligand in liver metastases of human colonic adenocarcinomas. Proc Natl Acad Sci USA 94:6420–6425
Niehans GA, Brunner T, Frizelle SP, et al (1997) Human lung carcinomas express Fas ligand. Cancer Res 57:1007–1012
Ungefroren H, Voss M, Jansen M, et al (1998) Human adenocarcinomas express Fas and Fas ligand yet are resistant to Fas-mediated apoptosis. Cancer Res 58:1741–1749
Nuñez G, Benedict MA, Hu Y, et al (1998) Caspases: the proteases of the apoptotic pathway. Oncogene 17:3237–3245
Tewari M, Quan LT, O’Rouke K, et al (1995) Yama/CPP32β, a mammalian homologue of CED-3, is a crmA-inhibitable protease that cleaves the death substrate poly ADP-ribose polymerase. Cell 81:801–809
Hoshi T, Sasano H, Kato K, et al (1998) Immunohistochemistry of Caspase3/CPP32 in human stomach and its correlation with cell proliferation and apoptosis. Anticancer Res 18:4347–4353
Krajewski S, Gascoyne RD, Zapata JM, et al (1997) Immunolocalization of ICE/ced-3-family protease, CPP-32 (caspase-3), in non-Hodgkin’s lymphomas, chronic leukemias, and reactive lymph nodes. Blood 89:3817–3825
Nakagawara A, Nakamura Y, Ikeda H, et al (1997) High levels of expression and nuclear localization of interleukin-1β converting enzyme (ICE) and CPP32 in favorable human neuroblastomas. Cancer Res 57:4578–4584
Ambrosini G, Adida C, Altieri DC (1997) A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma. Nat Med 3:917–921
Adida C, Berrebi D, Peuchmaur M, et al (1998) Anti-apoptosis gene, survivin, and prognosis of neuroblastoma. Lancet 351:882–883
Kawasaki H, Altieri DC, Lu C-D, et al (1998) Inhibition of apoptosis by survivin predicts shorter survival rates in colorectal cancer. Cancer Res 58:5071–5074
Lu CD, Altieri DC, Tanigawa N (1998) Expression of a novel antiapoptosis gene, survivin, correlated with tumor cell apoptosis and p53 accumulation in gastric carcinomas. Cancer Res 58:1808–1812
Grossman D, McNiff JM, Li F, et al (1999) Expression of the apoptosis inhibitor, survivin, in nonmelanoma skin cancer and gene targeting in a keratinocyte cell line. Lab Invest 79:1121–1126
Satoh K, Shimosegawa T, Masamune A, et al (1999) Fas ligand is frequently expressed in human pancreatic duct cell carcinoma. Pancreas 19:339–345
Satoh K, Kaneko K, Hirota M, et al (2000) The pattern of CPP 32/Caspase-3 expression reflects the biological behavior of the human pancreatic duct cell tumors. Pancreas (in press)
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2001 Springer Japan
About this paper
Cite this paper
Satoh, K., Masamune, A., Kaneko, K., Hirota, M., Satoh, A., Shimosegawa, T. (2001). Expression of Apoptosis-Related Factors in Human Pancreatic Duct Cell Carcinoma and Intraductal Papillary-Mucinous Tumor. In: Asakura, H., Aoyagi, Y., Nakazawa, S. (eds) Trends in Gastroenterology and Hepatology. Springer, Tokyo. https://doi.org/10.1007/978-4-431-67895-3_11
Download citation
DOI: https://doi.org/10.1007/978-4-431-67895-3_11
Publisher Name: Springer, Tokyo
Print ISBN: 978-4-431-67993-6
Online ISBN: 978-4-431-67895-3
eBook Packages: Springer Book Archive