Reactivation of proliferin gene expression is associated with increased angiogenesis in a cell culture model of fibrosarcoma tumor progression

Proliferin (PLF) is an angiogenic placental hormone. We now report that PLF gene expression can also occur in a progressive fibrosarcoma mouse tumor c ell model. PLF mRNA and protein are detectable at very low levels in cell l ines derived from the mild noninvasive stage of tumor development. Expressi on is greatly augmented in cell lines from the aggressively invasive stage of development, a stage at which the tumor becomes highly angiogenic, and P LF expression remains high in cell lines from the end stage of fibrosarcoma . Activator protein 1 factors present at high levels in the more invasive s tages of the tumor may in part allow for increased PLF expression, as cells from the mild stage in which c-jun and junB are stably expressed secrete l evels of PLF comparable to that of the advanced stages. Secreted PLF protei n is functionally important in tumor cell angiogenic activity, as demonstra ted by the reduction of angiogenic activity in fibrosarcoma cell culture me dium by immunodepletion of PLF. These results suggest that an extraembryoni c genetic program, which has evolved to support fetal growth, may be reacti vated in certain tumors and contribute to tumor growth.