Invasion and metastasis of a mammary tumor involves TGF‐β signaling

• Published in: International journal of cancer Vol. 91; no. 1; pp. 76 - 82
• Main Authors: McEarchern, Julie A., Kobie, James J., Mack, Vivian, Wu, Rita S., Meade‐Tollin, Linda, Arteaga, Carlos L., Dumont, Nancy, Besselsen, David, Seftor, Elisabeth, Hendrix, Mary J.C., Katsanis, Emmanuel, Akporiaye, Emmanuel T.
• Format: Journal Article
• Language: English
• Published: New York John Wiley & Sons, Inc 01.01.2001; Wiley-Liss
• Subjects: 4T1; Animals; Biological and medical sciences; Blotting, Northern; Blotting, Western; Cell Cycle - drug effects; Cell Division; Cell Movement - drug effects; Collagen - metabolism; Cross-Linking Reagents - pharmacology; Dissemination; DNA-Binding Proteins - metabolism; Dose-Response Relationship, Drug; Female; Flow Cytometry; Genes, Dominant; mammary cancer; Mammary Neoplasms, Animal - metabolism; Medical sciences; metastasis; Mice; Mice, SCID; Microscopy, Confocal; Neoplasm Invasiveness; Phenotype; Plasmids - metabolism; Receptors, Transforming Growth Factor beta - biosynthesis; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; Smad; TGF‐β; Transcription, Genetic; Transforming Growth Factor beta - genetics; Transforming Growth Factor beta - metabolism; Transforming Growth Factor beta1; Tumor cell; Tumor Cells, Cultured; Tumors; Transforming growth factor β; Cytokine; Rodentia; Metastasis; Malignant tumor; Mammary gland diseases; Signal transduction; Vertebrata; Mammalia; Mouse; Polypeptide; Animal; Dissemination; Established cell line; Mammary gland; Growth factor
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/1097-0215(20010101)91:1<76::AID-IJC1012>3.0.CO;2-8

Several studies have correlated escape from TGF‐β‐mediated cell cycle arrest with the tumorigenic phenotype. Most often, this escape from growth control has been linked to dysfunctional TGF‐β receptors or defects in the TGF‐β‐mediated SMAD signaling pathway. In this report, we found that highly metastatic 4T1 mammary carcinoma cells express functional TGF‐β receptors capable of initiating SMAD‐mediated transcription, yet are not growth inhibited by TGF‐β1. We further observed that TGF‐β directly contributes to the metastatic behavior of this cell line. Exposure to TGF‐β caused 4T1 cells to undergo morphological changes associated with the metastatic phenotype and invade more readily through collagen coated matrices. Furthermore, expression of a dominant negative truncated type II receptor diminished TGF‐β signaling and significantly restricted the ability of 4T1 cells to establish distant metastases. Our results suggest that regardless of 4T1 resistance to TGF‐β‐mediated growth inhibition, TGF‐β signaling is required for tumor invasion and metastases formation. Int. J. Cancer 91:76–82, 2001. © 2001 Wiley‐Liss, Inc.