Nerve growth factor stimulation of mouse embryonal carcinoma cell migration.

Embryonal carcinoma cells localize to a specific array of target tissues including the male submaxillary gland following intracardiac injection. These target tissues or conditioned medium derived from them have been shown to stimulate the in vitro migration of embryonal carcinoma cells. Here we show that in vitro migration of mouse embryonal carcinoma cells is induced by the simultaneous presence of two different components. One of these is a specific requirement for a fibronectin substrate. The other component is present in male submaxillary conditioned medium and may be nerve growth factor (NGF). Migration of embryonal carcinoma cells on a fibronectin substrate could be induced by purified NGF, but not epidermal growth factor, and submaxillary conditioned medium contained very high levels of nerve outgrowth activity which could be blocked by anti-NGF antibody. Only the high molecular weight 7S NGF complex was active in inducing migration, while the low molecular weight 2.5S NGF inhibited migration. Neither type of NGF or submaxillary conditioned medium stimulated the in vitro growth of embryonal carcinoma cells. 7S NGF thus differentially affects murine embryonal carcinoma cells by inducing cell motility but not cell division. That embryonal carcinoma cells require 7S NGF for their migration in vitro raises the interesting possibility that these cells may respond similarly in vivo, and be stimulated by tissue-specific high molecular weight NGF molecules to migrate or extravasate into the parenchyma of target organs.