Cancer Cells Neuraminidase

Cellular aggregation is closely involved in the differentiation and cancer processes since, in both cases, cellular aggregates release cells that migrate and adhere again to each other or to different cells. Because of our limited knowledge of the chemical structures at the surface of cells, most observations on the role of sialic acid residues in intercellular aggregates have been obtained indirectly by treatment of normal, transformed, or cancer cells with neuraminidase. No general mechanism... 

Sialic acid residues were found to be important in the transport of amino acids and proteins in cancer cells, since neuraminidase treatment of HeLa cells decreased the net accumulation of a-aminoisobutyric acid without altering the rate of efflux of preloaded cells (Brown and Michael, 1969), and the same treatment of L1210 leukemia cells inhibited the outward flow of proteins without influencing lysis or the release of nucleosides or sugars. Some relative specificity in the release of proteins was shown by disk-gel electrophoresis (Click et aL, 1966). 

Watkins, E., Jr., Ogata, Y., Anderson, L. L., Watkins, E., Ill, and Waters, M. F., 1971, Activation of host lymphocytes cultured with cancer cells treated with neuraminidase. Nature (Lond.) New Biol. 231 83. 

Nicolson, G. L. (1973). Neuraminidase unmasking and failure of trypsin to unmask -D-galactose-like sites on erythrocyte, lymphoma, and normal and virus-transformed fibroblast cell membranes. J. Natl. Cancer Inst. 50, 1443-1451. 

Sialidases are enzymes that catalyze the removal of terminal sialic acids from sialosides (56, 57). Human sialidases play pivotal roles in sialic acid metabolism (58). They relate to a number of disease states such as sialidosis (59-62) and cancer (63-65). Bacterial and viral play significant roles in the pathogenesis and pathology of bacterial and viral infections (66, 67). Viral sialidases such as neuraminidases of influenza virus catalyze the removal of sialic acid from the surface of infected host cells to release the newly formed progeny virus (68). 

In summary, tumor immunotherapy with neuraminidase-treated cells could improve medical treatment of cancer, if the following presuppositions are fulfilled (a) Low tumor burden or the tumor load has to be reduced by surgery, chemotherapy or irradiation, (b) a still immune-competent organism and (c) optimized doses of tumor cells and VCN, because—as Wilson (1974) has put it the greatest danger for clinical application of immunotherapy is the risk of stimulating tumor growth in a patient with only minimal residual disease . 

Currie, G. A., and Bagshawe, K. D., 1%9, Tumor specific immunogenecity of methyl-cholanthrene-induced sarcoma cells after incubation in neuraminidase, Brit. J. Cancer 23 141-149. 

In an attempt to determine whether this effect of neuraminidase could be applied to the clinical management of human cancer, Simmons and his collaborators (Simmons and Rios, 1971, 1972 Rios and Simmons, 1974) and others (Holland et al., 1972) inoculated tumor-bearing rodents with neuraminidase-treated tumor cells and used this procedure in combination with immunotherapy (Simmons and Rios, 1971 Holland... 

Rios, A., and Simmons, R. L., 1974, Active specific immunotherapy of minimal residual tumor Excision plus neuraminidase-treated tumor cells. Intern. J. Cancer 13 71. 

Rosenberg, S. A., and Schwarz, S., 1974, Murine autoantibodies to a cryptic membrane antigen Possible explanation for neuraminidase-induced increase in cell immunoge-nicity, J. Natl. Cancer Inst. 52 1151. 

Sethi, K. K., and Brandis, H., 1973, Neuraminidase induced loss in transplantability of murine leukaemia 1210, induction of immunoprotection and the transfer of induced immunity to normal DBA/2 mice by serum and peritoneal cells, Br. J. Cancer 27 106. 

Weiss, L., and Cudney, T. L., 1971, Some effects of neuraminidase on the in vitro interactions between spleen and mastocytoma (P815) cells, Int. J. Cancer 7 187. 

Vasudevan, D. M., Balakrishnan, K., and Talwar, G. P., 1970, Effect of neuraminidase on electrophoretic mobility and immune cytolysis of human uterine cervix carcinoma cells, Int. J. Cancer 6 506-516. 

Weiss, L., Fisher, B., and Fisher, E. R., 1974, Effect of neuraminidase on the distribution of intravenously injected walker tumor cells in rats. Cancer 34 680-683. 

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