|
|
|
|
|
|
||
|
|
||||
|
|
||||
|
||||
Immunology |
Department of Hematology and Oncology (C.D.R., A.Z.G., C.J.H., D.M.A) and Department of Anatomical Pathology (C.W.C.), Royal Children's Hospital, Flemington Road, Parkville 3052, Melbourne, Victoria, Australia
2 Address correspondence and reprint requests to David M. Ashley, Department of Haematology and Oncology, Royal Children's Hospital, Flemington Road, Parkville 3052, Melbourne, Victoria, Australia.
Abstract
Fas (APO-1/CD95/TNFRSF6) is a member of the tumor necrosis/nerve growth factor receptor family that signals apoptotic cell death in sensitive cells. Expression of Fas and its agonistic ligand (FasL/TNFSF6) was investigated in ex vivo pediatric brain tumor specimens of various histologic types. Fas expression was identified in all of the 18 tumors analyzed by flow cytometry and immunohistochemistry. FasL expression was identified in most of the 13 tumors analyzed by both Western analysis and immunohistochemistry. Nine of these tumor specimens were treated with either the agonistic anti-Fas antibody (APO-1) in combination with protein A or FasL in short-term cytotoxicity assays. Sensitivity to apoptosis induced by the topoisomerase II inhibitor, etoposide, was also assessed. Despite the presence of Fas, all the specimens analyzed demonstrated a high degree of resistance to Fas-mediated apoptosis. These 9 specimens also showed a high degree of resistance to etoposide. Only 2 of the 9 specimens were susceptible to etoposide-induced cell death, whereas only 3 were sensitive to Fas-mediated apoptosis. One brain tumor was sensitive to both Fas ligation and etoposide treatment. This contrasted with the high degree of susceptibility to both etoposide- and Fas-induced apoptosis observed in the reference Jurkat cell line. The results suggest that Fas expression may be a general feature of tumors of the CNS and that a significant degree of resistance to Fas-mediated apoptosis may exist in ex vivo pediatric brain tumor specimens.
References
Altman, D.G. (1991) Practical Statistics for Medical Research. London: Chapman and Hall.
Armitage, R.J. (1994) Tumor necrosis factor receptor superfamily members and their ligands. Curr. Opin. Immunol. 6,407 -413.[CrossRef][ISI][Medline]
Ashley, D.M., Kong, F.M., Bigner, D.D., and Hale, L.P.
(1998) Endogenous expression of transforming growth factor beta1
inhibits growth and tumorigenicity and enhances Fas-mediated apoptosis in a
murine high-grade glioma model. Cancer Res.
58,302
-309.
Bellgrau, D., Gold, D., Selawry, H., Moore, J., Franzusoff, A., and Duke, R.C. (1995) A role for CD95 ligand in preventing graft rejection. Nature 377,630 -632.[CrossRef][Medline]
Boldin, M.P., Mett, I.L., Varfolomeev, E.E., Chumakov, I.,
Shemer-Avni, Y., Camonis, J.H., and Wallach, D. (1995)
Self-association of the "death domains" of the p55 tumor necrosis
factor (TNF) receptor and Fas/APO-1 prompts signaling for TNF and Fas/APO-1
effects. J. Biol. Chem.
270,387
-391.
Boldin, M.P., Goncharov, T.M., Goltsev, Y.V., and Wallach, D. (1996) Involvement of MACH, a novel MORT1/FADD-interacting protease, in Fas/APO-1- and TNF receptor-induced cell death. Cell 85,803 -815.[CrossRef][ISI][Medline]
Cohen, M.E., and Duffner, P.K. (1994) Brain Tumors in Children: Principles of Diagnosis and Treatment. New York: Raven Press.
Davidson, W.F., Giese, T., and Fredrickson, T.N.
(1998) Spontaneous development of plasmacytoid tumors in mice
with defective Fas-Fas ligand interactions. J. Exp.
Med. 187,1825
-1838.
Duke, R.C., Franzusoff, A., and Bellgrau, D. (1996) CD95 ligand in graft rejection. Nature 379,682 -683.[Medline]
Frei, K., Ambar, B., Adachi, N., Yonekawa, Y., and Fontana, A. (1998) Ex vivo malignant glioma cells are sensitive to Fas (CD95/APO-1) ligand-mediated apoptosis. J. Neuroimmunol. 87,105 -113.[CrossRef][ISI][Medline]
Gratas, C., Tohma, Y., Barnas, C., Taniere, P., Hainaut, P., and
Ohgaki, H. (1998) Up-regulation of Fas (APO-1/CD95) ligand and
down-regulation of Fas expression in human esophageal cancer.
Cancer Res. 58,2057
-2062.
Griffith, T.S., Brunner, T., Fletcher, S.M., Green, D.R., and
Ferguson, T.A. (1995) Fas ligand-induced apoptosis as a mechanism
of immune privilege. Science
270,1189
-1192.
Griffith, T.S., Yu, X., Herndon, J.M., Green, D.R., and Ferguson, T.A. (1996) CD95-induced apoptosis of lymphocytes in an immune privileged site induces immunological tolerance. Immunity 5,7 -16.[CrossRef][ISI][Medline]
Hahne, M., Rimoldi, D., Schroter, M., Romero, P., Schreier, M.,
French, L.E., Schneider, P., Bornand, T., Fontana, A., Lienard, D., Cerottini,
J., and Tschopp, J. (1996) Melanoma cell expression of Fas
(APO-1/CD95) ligand: Implications for tumor immune escape.
Science 274,1363
-1366.
Hanabuchi, S., Koyanagi, M., Kawasaki, A., Shinohara, N.,
Matsuzawa, A., Nishimura, Y., Kobayashi, Y., Yonehara, S., Yagita, H., and
Okumura, K. (1994) Fas and its ligand in a general mechanism of
T-cell-mediated cytotoxicity. Proc. Natl. Acad. Sci.
U.S.A. 91,4930
-4934.
Huang, D.C., Hahne, M., Schroeter, M., Frei, K., Fontana, A.,
Villunger, A., Newton, K., Tschopp, J., and Strasser, A. (1999)
Activation of Fas by FasL induces apoptosis by a mechanism that cannot be
blocked by Bcl-2 or Bcl-x(L). Proc. Natl. Acad. Sci.
U.S.A. 96,14871
-14876.
Itoh, N., Tsujimoto, Y., and Nagata, S. (1993) Effect of Bcl-2 on Fas antigen-mediated cell death. J. Immunol. 151,621 -627.[Abstract]
Itoh, Y., Yonehara, S., Ishii, A., Yonehara, M., Mizushima, S., Sameshima, M., Hase, A., Seto, Y., and Nagata, S. (1991) The polypeptide encoded by the cDNA for human cell surface antigen Fas can mediate apoptosis. Cell 66,233 -243.[CrossRef][ISI][Medline]
Izumu, I., Mineura, K., Watanabe, K., and Kowada, M. (1993) Characterization and chemosensitivity of two cell lines derived from human glioblastomas. J. Neurooncol. 17,111 -121.[CrossRef][Medline]
Kawai, K., Serizawa, A., Hamana, T., and Tsutsumi, Y. (1994) Heat-induced antigen retrieval of proliferating cell nuclear antigen and p53 protein in formalin-fixed, paraffin-embedded sections. Pathol. Int. 44,759 -764.[ISI][Medline]
Kayagaki, N., Kawasaki, A., Ebata, T., Ohmoto, H., Ikeda, S.,
Inoue, S., Yoshino, K., Okumura, K., and Yagita, H. (1995)
Metaloprotease-mediated release of human Fas ligand. J. Exp.
Med. 182,1777
-1783.
Kayagaki, N., Yamaguchi, N., Nagao, F., Matsuo, S., Maeda, H.,
Okumura, K., and Yagita, H. (1997) Polymorphism of murine Fas
ligand that affects the biological activity. Proc. Natl. Acad. Sci.
U.S.A. 94,3914
-3919.
Kischkel, F.C., Hellbardt, S., Behrmann, I., Germer, M., Pawlita, M., Krammer, P.H., and Peter, M.E. (1995) Cytotoxicity-dependent APO-1 (Fas/CD95)-associated proteins form a death-inducing signaling complex (DISC) with the receptor. EMBO J. 14,5579 -5588.[ISI][Medline]
Leithauser, F., Dhein, J., Mechtersheimer, G., Koretz, K., Bruderlein, S., Henne, C., Schmidt, A., Debatin, K.M., Krammer, P.H., and Moller, P. (1993) Constitutive and induced expression of APO-1, a new member of the nerve growth factor/tumor necrosis factor receptor superfamily, in normal and neoplastic cells. Lab. Invest. 69,415 -429.[ISI][Medline]
Medema, J.P., Scaffidi, C., Kischkel, F.C., Shevchenko, A., Mann, M., Krammer, P.H., and Peter, M.E. (1997) FLICE is activated by association with the CD95 death-inducing signaling complex (DISC). EMBO J. 16,2794 -2804.[CrossRef][ISI][Medline]
Muzio, M., Chinnaiyan, A.M., Kischkel, F.C., O'Rourke, K., Shevchenko, A., Ni, J., Scaffidi, C., Bretz, J.D., Zhang, M., Gentz, R., Mann, M., Krammer, P.H., Peter, M.E., and Dixit, V.M. (1996) FLICE, a novel FADD-homologous ICE/CED-3-like protease, is recruited to the CD95 (Fas/APO-1) death-inducing signaling complex. Cell 85,817 -827.[CrossRef][ISI][Medline]
Nagata, S., and Golstein, P. (1995) The Fas death
factor. Science 267,1449
-1456.
O'Connell, J., O'Sullivan, G.C., Collins, J.K., and Shanahan, F.
(1996) The Fas counterattack: Fas-mediated T cell killing by
colon cancer cells expressing Fas ligand. J. Exp. Med.
184,1075
-1082.
Oehm, A., Behrmann, I., Falk, W., Pawlita, M., Maier, G., Klas, C., Li-Weber, M., Richards, S., Dhein, J., Trauth, B.C., Ponsting, H., and Krammer, P.H. (1992) Purification and molecular cloning of the APO-1 cell surface antigen, a member of the tumor necrosis factor/nerve growth factor receptor superfamily: sequence identity with Fas antigen. J. Biochem. 267,10709 -10715.
Oshimi, Y., Oda, S., Honda, Y., Nagata, S., and Miyazaki S. (1996) Involvement of Fas ligand and Fas-mediated pathway in the cytotoxicity of human natural killer cells. J. Immunol. 157,2909 -2915.[Abstract]
Rensing-Ehl, A., Frei, K., Flury, R., Matiba, B., Mariani, S.M., Weller, M., Aebischer, P., Krammer, P.H., and Fontana, A. (1995) Local Fas/APO-1 (CD95) ligand-mediated tumor cell killing in vivo. Eur. J. Immunol. 25,2253 -2258.[ISI][Medline]
Rensing-Ehl, A., Malipiero, U., Irmler, M., Tschopp, J., Constam, D., and Fontana, A. (1996) Neurons induced to express major histocompatibility complex class I antigen are killed via the perforin and not the Fas (APO-1/CD95) pathway. Eur. J. Immunol. 26,2271 -2274.[ISI][Medline]
Saas, P., Boucraut, J., Quiquerez, A.L., Schnuriger, V., Perrin,
G., Desplat-Jego, S., Bernard, D., Walker, P.R., and Dietrich, P.Y.
(1999) CD95 (Fas/APO-1) as a receptor governing astrocyte
apoptotic or inflammatory responses: A key role in brain inflammation?
J. Immunol. 162,2326
-2333.
Saas, P., Walker, P.R., Hahne, M., Quiquerez, A.L., Schnuriger, V., Perrin, G., French, L., Van Meir, E.V., de Tribolet, N.D., Tschopp, J., and Dietrich, P.Y. (1997) Fas ligand expression by astrocytoma in vivo: Maintaining immune privlege in the brain? J. Clin. Invest. 99,1173 -1178.[ISI][Medline]
Scaffidi, C., Fulda, S., Srinivasen, A., Friesen, C., Li, F., Tomaselli, K.J., Debatin, K.M., Krammer, P.H., and Peter, M.E. (1998) Two CD95 (APO-1/Fas) signaling pathways. EMBO J. 17,1675 -1687.[CrossRef][ISI][Medline]
Schneider, P., Holler, N., Bodmer, J.L., Hahne, M., Frei, K., Fontana, A., and Tschopp, J. (1998) Conversion of membrane-bound Fas(CD95) ligand to its soluble form is associated with downregulation of its proapoptotic activity and loss of liver toxicity. J. Exp. Med. 18,1205 -1213.
Singer, G.G., Carrera, A.C., Marshak-Rothstein, A., Martinez, C., and Abbas, A.K. (1994) Apoptosis, Fas and systemic autoimmunity: The MRL-lpr/lpr model. Curr. Opin. Immunol. 6, 913-920.[CrossRef][ISI][Medline]
Strand, S., Hofmann, W.J., Hug, H., Muller, M., Otto, G., Strand, D., Mariani, S.M., Stremmel, W., Krammer, P.H., and Galle, P.R. (1996) Lymphocyte apoptosis induced by CD95 (APO-1/Fas) ligand-expressing tumor cells — a mechanism of immune invasion? Nat. Med. 2,1361 -1366.[CrossRef][ISI][Medline]
Strasser, A., and Newton, K. (1999) FADD/MORT1, a signal transducer that can promote cell death or cell growth. Int. J. Biochem. Cell Biol. 31,533 -537.[CrossRef][ISI][Medline]
Suda, T., Takahashi, T., Goldstein, P., and Nagata, S. (1993) Molecular cloning and expression of the Fas ligand, a novel member of the tumor necrosis factor family. Cell 75,1169 -1178.[CrossRef][ISI][Medline]
Tachibana, O., Nakazawa, H., Lampe, J., Watanabe, K., Kleihues, P.,
and Ohgaki, H. (1995) Expression of Fas/APO-1 during the
progression of astrocytomas. Cancer Res.
55,5528
-5530.
Tanaka, M., Suda, T., Takahashi, T., and Nagata, S. (1995) Expression of the functional soluble form of human fas ligand in activated lymphocytes. EMBO J. 14,1129 -1135.[ISI][Medline]
Tohma, Y., Gratas, C., Van Meir, E.G., Desbaillets, I., Tenan, M., Tachibana, O., Kleihues, P., and Ohgaki, H. (1998) Necrogenesis and Fas/APO-1 (CD95) expression in primary (de novo) and secondary glioblastomas. J. Neuropathol. Exp. Neurol. 57,239 -245.[ISI][Medline]
Tounekti, O., Belehradek, J., Jr., and Mir, L.M. (1995) Relationships between DNA fragmentation, chromatin condensation, and changes in flow cytometry profiles detected during apoptosis. Exp. Cell Res. 217,506 -516.[CrossRef][ISI][Medline]
Trauth, B.C., Klas, C., Peters, A.M., Matzku, S., Moller, P., Falk,
W., Debatin, K.M., and Krammer, P.H. (1989) Monoclonal
antibody-mediated tumor regression by induction of apoptosis.
Science 245,301
-305.
Walker, P.R., Saas, P., and Dietrich, P.Y. (1997) Role of Fas ligand (CD95L) in immune escape: The tumor cell strikes back. J. Immunol. 158,4521 -4524.[Abstract]
Watanabe-Fukunaga, R., Brannan, C.I., Copeland, N.G., Jenkins, N.A., and Nagata, S. (1992) Lymphoproliferation disorder in mice explained by defects in Fas antigen that mediates apoptosis. Nature 356,314 -317.[CrossRef][Medline]
Weller, M., Frei, K., Groscurth, P., Krammer, P.H., Yonekawa, Y., and Fontana, A. (1994) Anti-Fas/APO-1 antibody-mediated apoptosis of cultured human glioma cells: Induction and modulation of sensitivity by cytokines. J. Clin. Invest. 94,954 -964.
Weller, M., Malipiero, U., Aguzzi, A., Reed, J.C., and Fontana, A. (1995a) Protooncogene bcl-2 gene transfer abrogates Fas/APO-1 antibody-mediated apoptosis of human malignant glioma cells and confers resistance to chemotherapeutic drugs and therapeutic irradiation. J. Clin. Invest. 95,2633 -2643.
Weller, M., Malipiero, U., Rensing-Ehl, A., Barr, P.J., and
Fontana, A. (1995b) Fas/APO-1 gene transfer for human malignant
glioma. Cancer Res. 55,2936
-2944.
Weller, M., Schuster, M., Pietsch, T., and Schabet, M. (1998) CD95 ligand-induced apoptosis of human medulloblastoma cells. Cancer Lett. 128,121 -126.[CrossRef][ISI][Medline]
Werner, M., Von Wasielewski, R., and Komminoth, P. (1996) Antigen retrieval, signal amplification and intensification in immunohistochemistry. Histochem. Cell Biol. 105,253 -260.[CrossRef][ISI][Medline]
Yagita, H., Seino, K., Kayagaki, N., and Okumura, K. (1996) CD95 ligand in graft rejection. Nature 379,682 .
Yonehara, S., Ishii, A., and Yonehara, M. (1989) A
cell-killing monoclonal antibody (anti-Fas) to a cell surface antigen
co-downregulated with the receptor of tumor necrosis factor. J.
Exp. Med. 169,1747
-1756.
This article has been cited by other articles:
|
|
 |
|
  S. Xia, E. M. Rosen, and J. Laterra Sensitization of Glioma Cells to Fas-Dependent Apoptosis by Chemotherapy-Induced Oxidative Stress Cancer Res., June 15, 2005; 65(12): 5248 - 5255. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
