Abstract
1. For a better understanding of the biological features of astrocytic tumors, we investigated apoptosis and its pathway, especially in the interaction between Fas and Fas ligand (FasL).
2. We examined the presence of apoptosis in human astrocytic brain tumors by terminal deoxynucleotidyl transferase (TdT)-mediated d-UTP-biotin nick end labeling (TUNEL) and then apoptotic index (AI) was calculated. We also examined the distribution of Fas and FasL-positive tumor cells immunohistochemically. Labeling index (LI) for Fas and FasL was calculated as Fas-LI and FasL-LI, respectively, and compared to AI.
3. Tumor cells expressing both Fas and FasL were TUNEL positive. Such cells were distributed sparsely in low-grade astrocytomas, but focally in glioblastomas. There was a close correlation among AI, Fas-LI, and FasL-LI, and astrocytic tumors with higher AI were associated with a longer survival time than that with lower AI.
4. It was concluded that the Fas system may be involved in the apoptosis of astrocytic tumors, and AI can be a useful parameter for assessing prognosis of astrocytic tumors.
Similar content being viewed by others
REFERENCES
Adams, J. C. (1981). Heavy metal intensification of DAB-based HRP reaction product. J. Histochem. Cytochem. 29:775.
Ellison, D.W., Steart, P.V., Gatter, K. C., and Weller, R.O. (1995). Apoptosis in cerebral astrocytic tumors and its relationship to expression of the bcl-2 and p53 proteins. Neuropathol. Appl. Neurobiol. 21:352–361.
Frankel, B., Longo, S. L., Kyle, M., Canute, G. W., and Ryken, T. C. (2001). Tumor Fas (APO-1/CD95) up-regulation results in increased apoptosis and survival times for rats with intracranial malignant gliomas. Neurosurgery 49:168–175.
Frankel, B., Longo, S. L., and Ryken, T. C. (1999). Human astrocytomas co-expressing Fas and Fas ligand also produce TGFβ2 and Bcl-2. J. Neurooncol. 44:205–212.
Fujita, T., and Kayama, T. (1997). Clinical and biological considerations regarding glioma based on the TUNELmethod and immunohistochemical staining using apoptosis-related antibodies. Brain Tumor Pathol. 14:97–102.
Gavrieli, Y., Sherman, Y., and Ben-Sasson, S. A. (1992). Identification programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J. Cell Biol. 119:493–501.
Gratas, C., Tohma, Y., Meir, E. G. V., Klein, M., Tenan, M., Ishii, N., Tachibana, O., Kleihues, O., and Ohgaki, H. (1997). Fas ligand expression in glioblastoma cell lines and primary astrocytic brain tumors. Brain Pathol. 7:863–869.
Hakuno, N., Koji, T., Yano, T., Kobayashi, N., Tsutsumi, O., Taketani, Y., and Nakane, P. K. (1996). Fas/APO-1/CD95 system as a mediator of granulosa cell apoptosis in ovarian follicle atresia. Endocrinology 137:1938–1948.
Hara, A., Hirayama, H., and Sasaki, N. (1990). Correlation between nuclear organizer region staining and Ki-67 immunostaining in human gliomas. Surg. Neurol. 33:320–324.
Heesters, M. A. A. M., Koudstaal, J., Go, K. G., and Molenaar, W. M. (1999). Analysis of proliferation and apoptosis in brain gliomas: Prognostic and clinical value. J. Neurooncol. 44:255–266.
Husain, N., Chiocca, E. A., Rainov, N., Louis, D. N., and Zervas, N. T. (1998). Co-expression of Fas and Fas ligand in malignant glial tumos and cell lines. Acta Neuropathol. 95:287–290.
Itoh, N., Yonehara, S., Ishii, A., Yonehara, M., Mizuushima, S.-I., 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.
Iwamoto, M., Koji, T., Makiyama, K., Kobayashi, N., and Nakane, P.K. (1996). Apoptosis of crypt epithelial cells in ulcerative colitis. J. Pathol. 180:152–159.
Kerr, J. F. R., Wyllie, A. H., and Currie, A. R. (1972). Apoptosis: A basic biological phenomenon with wide-ranging implications in tissue kinetics. Br. J. Cancer 26:239–257.
Kim, D. K., Hoyt, J., Bacci, C., Keles, G. E., Mass, M., Mayberg, M. R., and Berger, M. S. (1993). Detection of proliferating cell nuclear antigen in gliomas and adjacent resection margins. Neurosurgery 33:619–626.
Kleihues, P., Burger, P. C., and Scheithauer, B.W. (1993). Histological typing of tumors of the central nervous system. In World Health Organization (ed.), International Histological Classification of Tumors, 2nd edn., Springer, Berlin, Germany.
Koji, T., and Brenner, R. M. (1993). Localization of estrogen receptor messenger ribonucleic acid in rhesus monkey uterus by nonradioactive in situ hybridization with digoxigenin-labeled oligodeoxynucleotides. Endocrinology 132:382–392.
Koji, T., Kobayashi, N., Nakanishi, Y., Yoshii, A., Hashimoto, S., Shibata, Y., Anjiki, N., Yamamoto, R., Aoki, A., Ueda, T., Kanazawa, S., and Nakane, P. K. (1994). Immunohistochemical localization of Fas antigen in paraffin sections with rabbit antibodies against human synthetic Fas peptides. Acta Histochem. Cytochem. 27:459–463.
Korshunov, A., Golanov, A., Sycheva, R., and Pronin, I. (1999). Prognostic value of tumour associated antigen immunoreactivity and apoptosis in cerebral glioblastomas: An analysis of 168 cases. J. Clin. Pathol. 52:574–580.
Midis, G. P., Shen, Y., and Owen-Schaub, L. B. (1996). Elevated soluble Fas (sFas) levels in nonhematopoietic human malignancy. Cancer Res. 56:3870–3874.
Mita, E., Hayashi, N., Iio, S., Takehara, T., Hijioka, T., Kasahara, A., Fusamoto, H., and Kamada, T. (1994). Role of Fas ligand in apoptosis induced by hepatitis C virus infection. Biochem. Biophys. Res. Commun. 204:468–474.
Nakagawa, S., Shiraishi, T., Kihara, S., and Tabuchi, K. (1995). Detection ofDNAstrand breaks associated with apoptosis in human brain tumors. Virchows Arch. 427:175–179.
Saas, P., Walker, P. R., Hahne, M., Quiquerez, A. L., Schnuriger, V., Perrin, G., French, L., Meir, E. G. V., Tribolet, N. D., Tschopp, J., and Dietrich, P. Y. (1997). Fas ligand expression by astrocytoma in vivo: Maintaining immune privilege in the brain? J. Clin. Invest. 99:1173–1178.
Sentman, C. L., Shutter, J. R., Hockenbery, D., Kanagawa, O., and Korsmeyer, S. J. (1991). Bcl-2 inhibits multiple forms of apoptosis but not negative selection of thymocytes. Cell 67:879–888.
Shiffer, D., Cavalla, P., Migheli, A., Chio, A., Giordana, M. T., Marino, S., and Attanasio, A. (1995). Apoptosis and cell proliferation in human neuroepithelial tumors. Neurosci. Lett. 195:81–84.
Shiffer, D., Dutto, A., Cavalla, P., Chio, A., Migheli, A., and Piva, R. (1997). Role of apoptosis in the prognosis of oligodendroglioma. Neurochem. Int. 31:245–250.
Tachibana, O., Lampe, J., Kleihues, P., and Ohgaki, H. (1996). Preferential expression of Fas/APO 1 (CD95) and apoptotic cell death in perinecrotic cells of glioblastoma multiforme. Acta Neuropathol. 92:431–434.
Tohma, Y., Gratas, G., Meir, E. G. V., 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 glioblastoma. J. Neuropathol. Exp. Neurol. 57:239–245.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Fujita, H., Koji, T., Kitagawa, N. et al. Possible Involvement of Fas System in the Induction of Apoptosis in Human Astrocytic Brain Tumors. Cell Mol Neurobiol 22, 393–406 (2002). https://doi.org/10.1023/A:1021007503779
Issue Date:
DOI: https://doi.org/10.1023/A:1021007503779