Summary
Fluorescent neoglycoproteins were used to screen for the presence and sugar specificities of cell surface lectins in two human embryonal carcinoma cell lines. Efficient labeling correlated with extent of lectin-mediated uptake of neoglycoproteins, as measured by inhibition of DNA synthesis by drug-neoglycoprotein conjugates. These conjugates contain covalently linked carbohydrate moieties on the carriers to render them accessible to the membrane lectins, most effectively galactosides and α-glucosides. They furthermore contain chemically linked cytotoxic drugs (etoposide, cis-diamminedichloroplatinum II and methotrexate) which are intracellularly released after lysosomal breakdown of the carrier, as indicated by the effect of leupeptin. Sugars can confer a greater than 10-fold increase in cytotoxic capacity to the nonglycosylated carrier-drug conjugate, nearly reaching the level of toxicity of the freely diffusible drug. Two different neoglycoproteins, reacting with independently targeted membrane lectins, were shown to be useful in a model for combination chemotherapy. These results therefore suggest potential usefulness of custom-made glycosylated carriers in the targeting of therapeutic agents to human embryonal carcinoma cells.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Andrews PW, Bronson DL, Benham F, Strickland S, Knowles BB (1980) A comparative study of eight cell lines derived from human testicular teratocarcinoma. Int J Cancer 26:269
Bloch A, (1984) Induced cell differentiation in cancer therapy. Cancer Treat Rep 68:199
Bodmer JL, Dean RT (1985) Carrier potential of glycoporteins. Methods Enzymol 112:298
Bronson DL, Andrews PW, Solter D, Cervenka J, Lange PH, Fraley EE (1980) Cell line derived from a metastasis of a human testicular germ cell tumor. Cancer Res 40:2500
Calabresi P, Dexter DL, Heppner GH (1979) Clinical and pharmacological implications of cancer cell differentiation and heterogeneity. Biochem Pharmacol 28:1933
Chu BCF, Fan CC, Howell SB (1981) Activity of free and carrier-bound methotrexate against transport-deficient and high dihydrofolate dehydrogenase-containing methotrexate resistant L1210 cells. J Natl Cancer Inst 66:121
Das PK, Murray GJ, Zirzow GC, Brady RO, Barranger JJ (1985) Lectin-specific targeting of β-glucocerebrosidase to different liver cells via glycosylated liposomes. Biochem Med 33:124
Gabius HJ (1986) Endogenous lectins in tumors and the immune system. Cancer Inv (in press)
Gabius HJ, Engelhardt R, Casper J, Reile D, Schunacher S, Schmoll HJ, Graupner G, Cramer F (1985) Cell surface lectins of transplantable human teratocarcinoma cells: purification of a new mannan-specific endogeneous lectin. Tumor Biol 7:145
Gabius HJ, Engelhardt R, Casper J, Schmoll HJ, Nagel GA, Cramer F (1985) Comparison of endogenous lectins in human embryonic carcinoma and yolk sac carcinoma. Tumour Biol 7:471
Gabius HJ, Engelhardt R, Cramer F (1986) Endogenous tumor lectins: overview and perspectives. Anticancer Res 6:573
Gabius HJ, Engelhardt R, Sartoris DJ, Cramer F (1986) Pattern of endogenous lectins of a human sarcoma (Ewing's sarcoma) reveals differences to human normal tissues and tumors of epithelial and germ cell origin. Cancer Lett 31:139
Gabius HJ, Vehmeyer K, Engelhardt R, Nagel GA, Cramer F (1986) Carbohydrate-binding proteins of tumor lines with different growth properties. II. Changes in their pattern in clones of transformed rat fibroblasts of differing metastatic potential. Cell Tissue Res 246:515
Ho DH, Kanellopoulos KS, Brown NS, Issell BF, Bodey GP (1985) Radioimmunoassay for etoposide and teniposide. J Immunol Methods 85:5
Hurwitz E, Kashi R, Wilchek M (1982) Platinum-complexed antitumor immunoglobulins that specifically inhibit DNA synthesis of mouse tumor cells. J Natl Cancer Inst 69:47
Kanellos J, Pietersz GA, McKenzie IFC (1985) Studies of methotrexate-monoclonal antibody conjugates for immunotherapy. J Natl Cancer Inst 75:319
Kieda C, Roche AC, Monsigny M (1979) Lymphocyte membrane lectins. Direct visualization by the use of fluoresceinyl-glycosylated cytochemical markers. FEBS Lett 99:329
Lee YC, Townsend RR, Hardy MR, Lönngren J, Arnarp J, Haraldsson M, Lönn H (1983) Binding of synthetic oligesaccharides to the hepatic gal/galNAc lectin. Dependence on fine structural features. J Biol Chem 258:199
Loehrer PJ, Sledge GW, Einhorn LH (1985) Heterogeneity among germ cell tumors of the testis. Semin Oncol 12:304
McBroom CR, Samanen CH, Goldstein IJ (1972) Carbohydrate antigens: Coupling of carbohydrates to proteins by diazonium and phenylisothiocyanate reaction. Methods Enzymol 28:212
Monsigny M, Roche AC, Midoux P (1984) Uptake of neoglycoproteins via membrane lectin(s) of L1210 cells evidenced by quantitative flow cytofluorometry and drug targeting. Biol Cell 51:187
Roche AC, Barzilay M, Midoux P, Junqua S, Sharon N, Monsigny M (1983) Sugar-specific endocytosis of glycoproteins by Lewis lung carcinoma cells. J Cell Biochem 22:131
Schabel FM, Trader WW, Laster WR, Corbott TH, Griswold DP (1979) Cis-Dichlorodiammineplatinum. II. Combination chemotherapy and cross-resistance studies with tumors of mice. Cancer Treat Rep 63:1459
Schwartz BA, Gray GR (1977) Proteins containing reductively aminated disaccharides. Arch Biochem Biophys 181:542
Setaro F, Morley CGD (1976) A modified fluorometric method for the determination of microgram quantities of DNA from cell or tissue cultures. Anal Biochem 71:313
Stern PL (1984) Diferentiation antigens of teratomas and embryos. Br Med Bull 40:218
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Gabius, HJ., Bokemeyer, C., Hellmann, T. et al. Targeting of neoglycoprotein-drug conjugates to cultured human embryonal carcinoma cells. J Cancer Res Clin Oncol 113, 126–130 (1987). https://doi.org/10.1007/BF00391433
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00391433