Usefulness of glycosylated recombinant human lymphotoxin for growth inhibition of human and murine solid tumors and experimental metastasis in mice.
We have examined the antitumor and antimetastatic effects of native-type, glycosylated recombinant lymphotoxin (LT) on human and murine tumors transplanted in mice. The results reported here are as follows: (a) The in vivo antitumor spectrum of LT is not coincident with the in vitro study, and it has a wide antitumor spectrum and substantially inhibits the growth of human solid tumors, (b) When both syngeneic and nude mice are transplanted with Meth A tumor, the significant growth-inhibitory effect of LT is obtained in syngeneic mice, but the effect is quite small in nude mice regardless of the routes; LT attains the same degree of effectiveness as that in syngeneic mice, but at an 8 to 16 times higher dose. Furthermore, the pretreatment with anti-asialo-GM1 antibody inhibits the antitumor effects of LT in syngeneic mice, (c) In the pulmonary metastasis model induced by i.v. injection of Meth A cells, a high preventive effect of LT is obtained by systemic administration in syngeneic mice, but not in nude mice. In addition, the pretreatment with anti-asialo-GM1 antibody completely prevents the antimetastatic effect of LT, but also blocks that effect of control mice without LT treatment. In conclusion, LT appears to be a potent cytokine against tumor growth and metastasis in vivo. The differences between nude and syngeneic mice suggest the involvement of host immunity in the expression of LT function.
Funahashi
I
I
Biochemical Research Laboratories, Kanegafuchi Chemical Industry Co., Ltd., Hyogo, Japan.
Kawatsu
M
M
Kajikawa
T
T
Takeo
K
K
Asahi
T
T
Kakutani
T
T
Yamashita
T
T
Kawaharada
H
H
Watanabe
K
K
D000818:Animals; D005260:Female; D005677:G(M1) Ganglioside; D006028:Glycosphingolipids / Q000276:immunology; D006031:Glycosylation; D006801:Humans; D007116:Immunization, Passive; D008175:Lung Neoplasms / Q000517:prevention & control / Q000556:secondary; D008233:Lymphotoxin-alpha / Q000627:therapeutic use*; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy; D008546:Melanoma, Experimental / Q000188:drug therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000188:drug therapy*; D011994:Recombinant Proteins; D012513:Sarcoma, Experimental / Q000188:drug therapy; D014407:Tumor Cells, Cultured
D006028:Glycosphingolipids; D008233:Lymphotoxin-alpha; D011994:Recombinant Proteins; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside