Invasion and metastasis of a mammary tumor involves TGF-beta signaling

Several studies have correlated escape from TGF-beta -mediated cell cycle a rrest with the tumorigenic phenotype. Most often, this escape from growth c ontrol has been linked to dysfunctional TGF-beta receptors or defects in th e TGF-beta -mediated SMAD signaling pathway. In this report, we found that highly metastatic 4TI mammary carcinoma cells express functional TGF-beta r eceptors capable of initiating SMAD-mediated transcription, yet are not gro wth inhibited by TGF-beta1. We further observed that TGF-beta directly cont ributes to the metastatic behavior of this cell line. Exposure to TGF-beta caused 4TI cells to undergo morphological changes associated with the metas tatic phenotype and invade more readily through collagen coated matrices. F urthermore, expression of a dominant negative truncated type II receptor di minished TGF-beta signaling and significantly restricted the ability of 4TI cells to establish distant metastases, Our results suggest that regardless of 4TI resistance to TGF-beta -mediated growth inhibition, TGF-beta signal ing is required for tumor invasion and metastases formation. (C) 2001 Wiley -Liss, Inc.