Cancer-associated galactosyltransferase acceptor. Inhibition of transformed cell and tumor growth

A distinctive glycopeptide, which acts as an acceptor for a cancer-associated galactosyltransferase, has been detected in sera and effusions of patients with extensive carcinoma. Cancer-associated galactosyltransferase acceptor (CAGA) purified from human malignant effusions was tested for its effects on cell growth in vitro and in vivo. Addition of the glycopeptide to the media of cells growing in tissue culture significantly inhibited the attachment and growth of transformed cells but had minimal effect on nontransformed cells. Transformed hamster cells (BHKpy, BHKpygiv, Nilpy) and human malignant cells (BT-20 human breast, pancreatic and colonic carcinoma cells) were killed by the addition of as little as 0.5 microgram of acceptor (per ml of medium); whereas nontransformed counterparts did not show a significant change in growth or morphology. In vivo studies showed that the acceptor inhibited development and progression of tumors in hamsters inoculated with tumorigenic BHKpy cells and in nude mice inoculated with human carcinoma cells. Growth of tumors was inhibited 69--94% in animals given 20 micrograms of acceptor subcutaneously and 39--67% when acceptor was given intraperitoneally at the time of tumor cell inoculation. Administration of the acceptor after the development of palpable tumor (congruent to 0.5 cm) caused a 60--85% reduction in growth rate and, in some cases, actual reduction in size and disappearance of palpable tumor. These studies demonstrate that a galactosyltransferase glycopeptide acceptor purified from human malignant effusions produces selective inhibition of transformed cell growth in animal and tissue culture systems.