The stroma reaction has an important role in tumor growth, invasion, a
nd metastasis. In various invasive human carcinomas, as well as in a m
ouse model for tumor invasion, transcripts encoding the transcription
factor c-Ets1 were detected within stromal fibroblasts, whereas they w
ere absent in epithelial tumor cells. This expression of c-Ets1 was of
ten increased in fibroblasts directly adjacent to neoplastic cells. En
dothelial cells of stromal capillaries were also positive for c-Ets1 e
xpression. In contrast, fibroblasts of corresponding noninvasive lesio
ns and of normal tissues were consistently negative. In cultured human
fibroblasts stimulated by basic fibroblast growth factor and tumor ne
crosis factor alpha, the expression of c-Ets1 correlated with the accu
mulation of transcripts for potential target genes, collagenase-1 and
stromelysin-1. The same correlation was observed in some of the invasi
ve carcinomas investigated. These results suggest that c-Ets1 particip
ates in the regulation of tumor invasion in vivo.