Transfection of glioma cells with the neural-cell adhesion molecule NCAM: Effect on glioma-cell invasion and growth in vivo
Corresponding Author
Klaus Edvardsen
Research Center for Medical Biotechnology, Protein Laboratory, University of Copenhagen, Panum Institute, DK-2200 Copenhagen, Denmark
Research Center for Medical Biotechnology, Protein Laboratory, University of Copenhagen, Panum Institute, DK-2200 Copenhagen, DenmarkSearch for more papers by this authorPaal-Henning Pedersen
The Gade Institute, Department of Pathology, University of Bergen, N-5021 Haukeland Hospital, Bergen, Norway
Search for more papers by this authorRolf Bjerkvig
The Gade Institute, Department of Pathology, University of Bergen, N-5021 Haukeland Hospital, Bergen, Norway
Department of Anatomy and Cell Biology, University of Bergen, Bergen, Norway
Search for more papers by this authorGregers G. Hermann
Department of Tumor Cell Biology, Danish Cancer Society, Strandboulevarden 49, DK-2100 Copenhagen, Denmark
Search for more papers by this authorJesper Zeuthen
Department of Tumor Cell Biology, Danish Cancer Society, Strandboulevarden 49, DK-2100 Copenhagen, Denmark
Search for more papers by this authorOle Didrik Laerum
The Gade Institute, Department of Pathology, University of Bergen, N-5021 Haukeland Hospital, Bergen, Norway
Search for more papers by this authorFrank S. Waish
Department of Experimental Pathology, UMDS, Guy's Hospital, London Bridge, London SE1 9RT, UK
Search for more papers by this authorElisabeth Bock
Research Center for Medical Biotechnology, Protein Laboratory, University of Copenhagen, Panum Institute, DK-2200 Copenhagen, Denmark
Search for more papers by this authorCorresponding Author
Klaus Edvardsen
Research Center for Medical Biotechnology, Protein Laboratory, University of Copenhagen, Panum Institute, DK-2200 Copenhagen, Denmark
Research Center for Medical Biotechnology, Protein Laboratory, University of Copenhagen, Panum Institute, DK-2200 Copenhagen, DenmarkSearch for more papers by this authorPaal-Henning Pedersen
The Gade Institute, Department of Pathology, University of Bergen, N-5021 Haukeland Hospital, Bergen, Norway
Search for more papers by this authorRolf Bjerkvig
The Gade Institute, Department of Pathology, University of Bergen, N-5021 Haukeland Hospital, Bergen, Norway
Department of Anatomy and Cell Biology, University of Bergen, Bergen, Norway
Search for more papers by this authorGregers G. Hermann
Department of Tumor Cell Biology, Danish Cancer Society, Strandboulevarden 49, DK-2100 Copenhagen, Denmark
Search for more papers by this authorJesper Zeuthen
Department of Tumor Cell Biology, Danish Cancer Society, Strandboulevarden 49, DK-2100 Copenhagen, Denmark
Search for more papers by this authorOle Didrik Laerum
The Gade Institute, Department of Pathology, University of Bergen, N-5021 Haukeland Hospital, Bergen, Norway
Search for more papers by this authorFrank S. Waish
Department of Experimental Pathology, UMDS, Guy's Hospital, London Bridge, London SE1 9RT, UK
Search for more papers by this authorElisabeth Bock
Research Center for Medical Biotechnology, Protein Laboratory, University of Copenhagen, Panum Institute, DK-2200 Copenhagen, Denmark
Search for more papers by this authorAbstract
The tumor growth and the invasive capacity of a rat glioma cell line (BT4Cn) were studied after transfection with the human transmembrane 140-kDa isoform of the neural-cell adhesion molecule, NCAM. After s.c. injection, the NCAM-transfected cells showed a slower growth rate than the parent cell line (BT4Cn). Upon intracerebral implantation with BT4Cn cells and different clones of NCAM-transfected cells, all animals developed neurological symptoms within 13-16 days. However, the tumors showed different growth characteristics. The NCAM-transfected BT4Cn cells were localized in the region of the injection site, with a sharply demarcated border between the tumor and brain tissue. In contrast, the parental cell line showed single-cell infiltration and more pronounced destruction of normal brain tissue. Using a 51Cr-release assay, spleen cells from rats transplanted with BT4Cn tumor cells generally showed a lower cytotoxic response than the spleen cells from rats transplanted with the transfected variants of BT4Cn cells, indicating that the transfection procedure in itself mediated an activation of the immune system. The present data suggest that NCAM may influence the malignant behavior of rat glioma cells in vivo. © 1994 Wiley-Liss, Inc.
References
- Andersson, A. M., Moran, N., Gaardsvoli, H., Linnemann, D., Bjerkvig, R., Laerum, O. D. and Bock, E., Characterization of NCAM expression and function in BT4C and BT4Cn glioma cells. Int. J. Cancer, 47, 124–129 (1991).
- Aoki, J., Umeda, M., Takio, K., Titani, K., Utsumi, H., Sasaki, M. and Inoue, K., Neural cell adhesion molecule mediates contact-dependent inhibition of growth of near-diploid mouse fibroblast cell line m5s/1M. J. Cell Biol., 115, 1751–1761 (1991).
- Bernstein, J. J., Goldberg, W. J. and Laws, E. R., Jr., Human malignant astrocytoma xenografts migrate in rat brain: a model for central nervous system cancer research. J. Neurosci. Res., 22, 134–143 (1989).
- Bjerkvig, R., Laerum, O. D. and Mella, O., Glioma cell interactions with fetal rat brain aggregates in vitro and with brain tissue in vivo. Cancer Res., 46, 4071–4079 (1986).
- Bock, E., Cell-cell adhesion molecules. Biochem. Soc. Trans., 19, 1076–1080 (1991).
- Brady-Kalnay, S. M., Boghaert, E. R., Zimmer, S., Soll, D. R. and Brackenbury, R., Invasion by WC5 rat cerebellar cells is independent of RSV-induced changes in growth and adhesion. Int. J. Cancer, 49, 239–245 (1991).
- Couldwell, W. T., De Tribolet, H., Antel, J. P., Gauthier, T. and Kuppner, M. C., Adhesion molecules and malignant gliomas: implications for tumorigenesis. J. Neurosurg., 76, 782–791 (1992).
- Doherty, P., Ashton, S. V., Moore, S. E. and Walsh, F. S., Morphoregulatory activities of NCAM and N-cadherin can be accounted for by G protein-dependent activation of L- and N-type neuronal Ca2+ channels. Cell, 67, 21–33 (1991).
- Druckrey, H., Genotypes and phenotypes of ten inbred strains of BD-rats. Arzneim. Forsch., 21, 1274–1278 (1971).
- Edelman, G. and Crossin, K. L., Cell adhesion molecules: implications for a molecular histology. Ann. Rev. Biochem., 60, 155–190 (1991).
- Edvardsen, K., Brünner, N., Spang-Thomsen, M., Walsh, F. S. and Bock, E., Migratory, invasive and metastatic capacity of NCAM transfected rat glioma cells. Int. J. devel. Neurosci., 11, 681–691 (1993a).
- Edvardsen, K., Chen, W., Rucklidge, G., Walsh, F. S., Öbrink, B. and Bock, E., Transmembrane NCAM, but not glycosyl-phosphatidylinositol anchored NCAM, down-regulates secretion of matrix metalloprateinases. Proc. nat. Acad. Sci. (Wash.), 90, 11463–11467 (1993b).
- Fantinl, J., Guo, X. J., Marvaldi, J. and Rougon, G., Suramine inhibits proliferation of rat glioma cells and alters N-CAM cell surface expression. Int. J. Cancer, 45, 554–561 (1991).
- Goridis, C. and Brunet, J.-F., NCAM: structural diversity, function and regulation of expression. Sem. Cell Biol., 3, 189–197 (1992).
- Gunning, P., Leavitt, J., Muscat, G., Ng, S. Y. and Kedes, L., A human beta-actin expression vector system directs high-level accumulation of antisense transcripts. Proc. nat. Acad. Sci. (Wash.), 84, 4831–4835 (1987).
- Ibsen, S., Berezin, V., Nørgaard-Pedersen, B. and Bock, E., Enzyme-linked immunosorbent assay of the D2-glycoprotein. J. Neurochem., 41, 356–362 (1983).
- Lahmmli, U. K., Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature (Land.), 227, 680–685 (1970).
- Laerum, O. D., Rajewsky, M. F., Schachner, M., Stavrou, D., Haglid, K. H. and Haugen, A., Phenotypic properties of neoplastic cell lines developed from fetal rat brain cells in culture after exposure to ethylnitrosourea in vivo. Z. Krebsforsch., 89, 273–295 (1977).
- Lanier, L. L., Chang, C., Azuma, M., Ruitenberg, J. J., Hemperly, J. J. and Phillips, J. H., Molecular and functional analysis of human natural killer cell-associated neural cell adhesion molecule (N-CAM/CD 56). J. Immunol., 146, 4421–4426 (1991).
- Lanier, L. L., Testi, R., Bindl, J. and Phillips, J. H., Identity of Leu-19 (CD 56) leukocyte differentiation antigen and neural cell adhesion molecule. J. exp. Med., 169, 2233–2238 (1989).
- Marienhagen, K., Pedersen, P.-H., Terzis, A.-J., Laerum, O. D., Arnold, H. and Bjerkvig, R., Interactions between fetal rat brain cells anti mature brain tissue in vivo and in vitro. Neuropathol. appl. Neurobiol., (1994). (In press).
- Mella, O., Hyperthermia or BCNU alone or combined in BDIX rats with BT4An tumours. Effects of single or two equal fractions at different intervals. In Vivo, 2, 307–312 (1988).
- Mella, O., Bjerkvio, R., Schem, B.-C., Dahl, O. and Laerum, O. D., A cerebral glioma model for experimental therapy and in vivo invasion studies in syngeneic BD IX rats. J. Neurooncol, 9, 93–104 (1990).
- Pedersen, P. H., Marienhagen, K., Mørk, S. and Bjerkvig, R., The migratory pattern of fetal rat brain cells and human glioma cells in the adult brain. Cancer Res., 53, 5158–5165 (1993).
- Rao, J. S., Steck, P. A., Mohanam, S., Stetler-Stevenson, W. G., Liotta, L. A. and Sawaya, R., Elevated levels of Mr 92.000 type-IV collagenase in human brain tumors. Cancer Res., 53, 2208–2211 (1993).
- Rucklidge, G. J., Dean, V., Robins, S. P., Mella, O. and Bjerkvig, R., Immunolocalization of extracellular matrix proteins during brain tumor invasion in BD IX rats. Cancer Res., 49, 5419–5423 (1989).
-
Sambrook, J.,
Fritsh, E. F. and
Maniatis, T.,
Molecular cloning: a laboratory manual,
2nd ed.,
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY
(1989).
10.1111/j.1095-8312.1996.tb01434.x Google Scholar
- Schuch, U., Lohse, M. J. and Schachner, M., Neural cell adhesion molecules influence second messenger systems. Neuron, 3, 13–20 (1989).
- Spang-Thomsen, M., Nielsen, A. and Visfeldt, J., Growth curves of three human malignant tumors transplanted to nude mice. Exp. Cell Biol., 48, 138–154 (1980).
- Thiery, J. P., Duband, J. L., Rutishauser, U. and Edelman, G. M., Cell adhesion molecules in early chicken embryogenesis. Proc. nat. Acad. Sci. (Wash.), 79, 6737–6741 (1982).
- Walsh, F. S., Parekh, R. B., Moore, S. E., Dickson, G., Barton, C. H., Gower, H. J., Dwek, R. A. and Rademacher, T. W., Tissue specific O-linked glycosylation of the neural cell adhesion molecule (N-CAM). Development, 105, 803–811 (1989).