Growth response in athymic nude mice to transplanted growth hormone-secreting rat pituitary tumor cells.

Abstract

Clonal cell lines originally derived from a somatotropic rat pituitary tumor were grafted sc into athymic nude mice, and the growth response induced in the graft carriers was examined. When at least 106 rat tumor cells were injected per mouse, virtually all mice developed slow growing, nonmetastasizing tumors at the injection site. In immature nude mice, the somatotropic effect of the rat GH secreted by the growing tumor was clearly evident, as body weight continued to increase well beyond that of control littermates. Nude mice with a final body weight of over 60 g were regularly produced in this manner. The action of the rat GH in the nude mouse carriers was generalized, as shown by the fact that the gigantic mice resulting from the xenografts maintained apparently normal balanced physical proportions. Exceptionally, however, the islets of Langerhans in the host pancreas showed even greater hypertrophy, presumably due to the known anti-insulin activity of GH. The rat pituitary tumor cells were shown to synthesize and secrete a protein which was precipitated by an antiserum against rat GH and which comigrated with authentic rat GH when analyzed by sodium dodecyl sulfate-acrylamide electrophoresis. Through serial transplantation in nude mice, the tumor cells retained their functional and tumorigenic properties. These results demonstrate that rat GH is active in the mouse, and suggest also that the athymic nude mouse should be useful for the development of other xenogeneic tumor lines that secrete GH.