Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Kocaturk B

PROVIDER: S-EPMC3710867 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Kocatürk Begüm B Van den Berg Yascha W YW Tieken Chris C Mieog J Sven D JS de Kruijf Esther M EM Engels Charla C CC van der Ent Martijn A MA Kuppen Peter J PJ Van de Velde Cornelis J CJ Ruf Wolfram W Reitsma Pieter H PH Osanto Susanne S Liefers Gerrit-Jan GJ Bogdanov Vladimir Y VY Versteeg Henri H HH

Proceedings of the National Academy of Sciences of the United States of America 20130625 28

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 promote ...[more]

PMID: 23801760

Similar Datasets

Project description:Heart failure and cancer are currently the deadliest diseases in the Western world, posing the most pressing clinical challenges that remain unmet today. Both conditions share similar risk factors, including age, genetics, lifestyle, chronic inflammation, stress, and more. Furthermore, medications that are being used to counteract cancer frequently result in cardiotoxicity and the spontaneous emergence of heart failure. Thus, heart failure and cancer display an intimate connection and share similarities. Recent studies show that cardiac remodeling and heart failure promote cancer progression and metastasis. Using three different mouse models for heart failure revealed that the communication between the remodeled heart and the tumor is facilitated through multiple secreted factors. Among these factors, Periostin was consistently found to be elevated in all models and was shown to be required in vitro. Yet, whether Periostin is necessary for tumor promotion in vivo is unknown. Towards this end, we examined tumor promotion in mice lacking Periostin following transverse aortic constriction (TAC). Despite the loss of Periostin, tumor growth was promoted in the TAC-operated mice. This likely occurred due to increased levels of various cytokines and growth factors in Periostin KO mice. Many of these factors are potential ligands of Integrin receptors. Therefore, we next studied the role of Integrin receptors in the tumor-promotion phenotype following heart failure. We generated cancer cells with an Integrin β1 loss of function mutation and examined tumor growth in the presence and absence of heart failure. Integrin β1 KO cancer cells fail to display cardiac-remodeling-dependent tumor-promotion. Interestingly, a previous study showed that renal cell carcinoma cells (Renca) fail to be promoted following a myocardial infarction. Consistently, we show that Renca cells do not respond to secreted factors derived from the failing heart both in vitro and in vivo. Interestingly, Renca cells display low basal mRNA levels of Integrin β1 which may explain the inability of heart failure to promote their growth. The findings may have significant clinical relevance to cardio-oncology patients who suffer from cancers with high levels of Integrin β1. Chemotherapy leading to cardiotoxicity in these patients may generate a vicious cycle with poor prognosis.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets