Journal Article

Alternatively spliced tissue factor promotes breast cancer growth in a β1 integrin-dependent manner

Liefers, Gerrit-Jan, Tieken, Chris, Engels, Charla C., Kocatürk, Begüm, Kuppen, Peter J., Versteeg, Henri H., van der Ent, Martijn A., Van de Velde, Cornelis J., Reitsma, Pieter H., Van den Berg, Yascha W., Ruf, Wolfram, Osanto, Susanne, Bogdanov, Vladimir Y., de Kruijf, Esther M., Mieog, J. Sven D.

2013

Overview

Full-length tissue factor (flTF), the coagulation initiator, is overexpressed in breast cancer (BrCa), but associations between flTF expression and clinical outcome remain controversial. It is currently not known whether the soluble alternatively spliced TF form (asTF) is expressed in BrCa or impacts BrCa progression. We are unique in reporting that asTF, but not flTF, strongly associates with both tumor size and grade, and induces BrCa cell proliferation by binding to β1 integrins. asTF promotes oncogenic gene expression, anchorage-independent growth, and strongly up-regulates tumor expansion in a luminal BrCa model. In basal BrCa cells that constitutively express both TF isoforms, asTF blockade reduces tumor growth and proliferation in vivo. We propose that asTF plays a major role in BrCa progression acting as an autocrine factor that promotes tumor progression. Targeting asTF may comprise a previously unexplored therapeutic strategy in BrCa that stems tumor growth, yet does not impair normal hemostasis.

• Publisher: National Academy of Sciences,National Acad Sciences
• Subject: Adult / Alternative Splicing / Angiogenesis / Animals / Antibodies / autocrine signaling / Biological Sciences / Breast cancer / breast neoplasms / Breast Neoplasms - genetics / Breast Neoplasms - pathology / CD29 antigen / Cell growth / Cell Line, Tumor / Cell lines / Cell Proliferation / coagulation / Endothelial cells / Female / gene expression / hemostasis / Humans / Integrin beta1 - physiology / Integrins / Mice / Middle Aged / Proteins / stems / Thromboplastin - genetics / Thromboplastin - physiology / Tumors