The trefoil factor 3 (TFF3) protein protects and maintains the integrity of the epithelial surface in the normal breast. New research has found that while TFF3 protein expression is higher in well-differentiated low grade tumors and therefore associated with features of a good prognosis, it has a more sinister role in breast cancer invasion and metastasis. The report is published in the March issue of the American Journal of Pathology.
"Our findings suggest that TFF3 is regulated by estrogen and has beneficial properties in breast epithelia," says lead investigator Felicity E.B. May, PhD, of the Northern Institute for Cancer Research and the Department of Pathology at Newcastle University, UK. "We propose that early during breast tumorigenesis, TFF3 retains its association with normal functionality of breast epithelial cells. Subsequently, with the loss of tumor cell differentiation, its function is subverted to promote the development of tumors and infiltration and lymph node metastasis."
To determine the role of TFF3 in breast cancer, researchers measured its level in tissue samples from normal breasts, benign breast lesions, in situ carcinomas, invasive carcinomas, and involved lymph nodes. TFF3 was expressed in the majority of benign and malignant breast lesions studied. Well-differentiated tumor types expressed higher levels of TFF3. There was a positive association between TFF3 protein expression and microvessel density, suggesting that it stimulates angiogenesis in breast tumors.
A striking finding of the study is the strength and consistency of the association between TFF3 expression and a more metastatic phenotype in invasive breast cancer. TFF3 was expressed at higher levels in primary tumors with associated metastasis, and its expression was higher in malignant cells that have metastasized away from those within the primary tumor. There appears to be a switch in the normal polarized secretion of TFF3 in invasive cancer, which allows it to exert invasion-promoting effects.
The study suggests that TFF3 may be one of the genes that mediate the various effects of estrogens in breast cancer. "The paradox remains, however, for both the estrogen receptor and TFF3, that they contribute to the normal physiology of the breast epithelium yet are involved in the progression of cancer," notes Dr. May.
Importantly, the investigators also evaluated the potential of TFF3 as a biomarker of lymphovascular invasion and lymph node metastasis. They found that TFF3 had greater predictive power than other markers analyzed, including tumor grade, age, tumor size and type, and estrogen and progesterone receptor status. "Our study reinforces the view that TFF3 expression merits evaluation as a prognostic biomarker and as a predictive marker of response to therapy," concludes Dr. May. "It is probable that its malign effects will be mitigated by adjuvant endocrine therapy in women with hormone-responsive cancers. However, the usefulness of TFF3 as a marker of hormone responsiveness needs to be evaluated."
The article is "TFF3 Is a Normal Breast Epithelial Protein and Is Associated with Differentiated Phenotype in Early Breast Cancer but Predisposes to Invasion and Metastasis in Advanced Disease," by A.R.H. Ahmed, A.B. Griffiths, M.T. Tilby, B.R. Westley, and F.E.B. May (doi: 10.1016/j.ajpath.2011.11.022). It will appear in The American Journal of Pathology, Volume 180, Issue 3 (March 2012) published by Elsevier.
David Sampson | EurekAlert!
ECG procedure indicates whether an implantable defibrillator will extend a patient's life
02.09.2019 | Technische Universität München
Fracking prompts global spike in atmospheric methane
14.08.2019 | European Geosciences Union
A new research project at the TH Mittelhessen focusses on the development of a novel light weight design concept for leisure boats and yachts. Professor Stephan Marzi from the THM Institute of Mechanics and Materials collaborates with Krake Catamarane, which is a shipyard located in Apolda, Thuringia.
The project is set up in an international cooperation with Professor Anders Biel from Karlstad University in Sweden and the Swedish company Lamera from...
Superconductivity has fascinated scientists for many years since it offers the potential to revolutionize current technologies. Materials only become superconductors - meaning that electrons can travel in them with no resistance - at very low temperatures. These days, this unique zero resistance superconductivity is commonly found in a number of technologies, such as magnetic resonance imaging (MRI).
Future technologies, however, will harness the total synchrony of electronic behavior in superconductors - a property called the phase. There is currently a...
How do some neutron stars become the strongest magnets in the Universe? A German-British team of astrophysicists has found a possible answer to the question of how these so-called magnetars form. Researchers from Heidelberg, Garching, and Oxford used large computer simulations to demonstrate how the merger of two stars creates strong magnetic fields. If such stars explode in supernovae, magnetars could result.
How Do the Strongest Magnets in the Universe Form?
A hot, molten Earth would be around 5% larger than its solid counterpart. This is the result of a study led by researchers at the University of Bern. The difference between molten and solid rocky planets is important for the search of Earth-like worlds beyond our Solar System and the understanding of Earth itself.
Rocky exoplanets that are around Earth-size are comparatively small, which makes them incredibly difficult to detect and characterise using telescopes. What...
Scientists at the Max Planck Institute for Chemical Physics of Solids in Dresden, Princeton University, the University of Illinois at Urbana-Champaign, and the University of the Chinese Academy of Sciences have spotted a famously elusive particle: The axion – first predicted 42 years ago as an elementary particle in extensions of the standard model of particle physics.
The team found signatures of axion particles composed of Weyl-type electrons (Weyl fermions) in the correlated Weyl semimetal (TaSe₄)₂I. At room temperature,...
02.10.2019 | Event News
02.10.2019 | Event News
19.09.2019 | Event News
14.10.2019 | Physics and Astronomy
14.10.2019 | Earth Sciences
14.10.2019 | Health and Medicine