Inhibition of primary and metastatic tumor growth in mice by cancer-associated galactosyltransferase acceptor.
The antitumor activity of a glycopeptide purified from human malignant effusion, termed cancer-associated galactosyltransferase acceptor (CAGA), was assessed in BALB/c mice bearing primary and metastatic tumors. Initial studies with the fast-growing KA31 and slow-growing KB521 Kirsten sarcoma-transformed mouse fibroblast cell lines confirmed their tumorigenicity and metastatic potential. Inoculation of 1 X 10(5) KA31 cells s.c. resulted in palpable tumor formation in recipient animals within 14 days and death within 42 days from primary tumor growth (mean survival, 26 days; total survival, 0%). Inoculation of the slower-growing KB521 resulted in tumor formation in 85% of recipients, and tumor-bearing animals succumbed within 56 days after primary inoculation (mean survival, 48 days; total survival, 15%). Administration of CAGA by i.p. injection as a single dose or series of five daily doses (each 50 micrograms) inhibited primary tumor growth by 35 to 68% in animals receiving KA31 cells and by 25 to 70% in animals receiving KB521 cells. CAGA increased mean survival 50% from 26 to 38 days and total survival from 0 to 27% in animals bearing KA31-derived primary tumors. In animals bearing KB521-derived tumors, CAGA increased mean survival from 48 to 90 days and total survival from 15 to 50%. Similarly, CAGA was also found to significantly inhibit formation of pulmonary metastases in animals after excision of primary tumors. CAGA administration reduced death from metastatic deposits by 55 to 66% in animals initially inoculated with the KA31 cell line and by 58 to 90% in animals initially bearing primary tumors derived from the KB521 line. There was a corresponding decrease in the number of metastatic deposits per lung after administration of CAGA. Thus, CAGA appears to have potential antitumor activity against tumors with a range of growth rates and appears to inhibit both primary and metastatic tumor growth.
D000818:Animals; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D005700:Galactosyltransferases / Q000627:therapeutic use*; D006020:Glycopeptides / Q000627:therapeutic use*; D007708:Kirsten murine sarcoma virus / Q000235:genetics; D008175:Lung Neoplasms / Q000556:secondary / Q000628:therapy; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis; D012513:Sarcoma, Experimental / Q000628:therapy*
D006020:Glycopeptides; C018069:galactosyltransferase acceptor; D005700:Galactosyltransferases