The most deadly aspect of breast cancer is metastasis. It spreads cancer cells throughout the body. Researchers at the University and the University Hospital of Basel have now discovered a substance that suppresses the formation of metastases. In the journal Cell, the team of molecular biologists, computational biologists, and clinicians reports on their interdisciplinary approach.
The development of metastasis is responsible for more than 90% of cancer-related deaths, and patients with a metastatic disease are considered incurable.
The image represents an artistic coloration of a cluster of circulating tumor cells (CTCs), isolated from the blood of a patient with breast cancer, trapped on a microfluidic device.
© M Oeggerli / Micronaut 2018, supported by Pathology-, C-CINA / Biozentrum-, and I Krol, and N Aceto, Faculty of Medicine-, University Hospital and University Basel.
The interdisciplinary team led by Prof. Nicola Aceto from the Department of Biomedicine at the University of Basel has identified a drug that suppresses the spread of malignant cancer cells and their metastasis-seeding ability.
Precursors of metastases: Circulating tumor cell clusters
Circulating tumor cells (CTCs) are cancer cells that leave a primary tumor and enter the bloodstream, on their way to seeding distant metastases. These so-called CTCs can be found in the blood of patients as single cells or cell clusters. CTC clusters are the precursors of metastases.
The Basel research team has discovered that CTC cluster formation leads to key epigenetic changes that facilitate metastasis seeding. These changes enable CTC clusters to mimic some properties of embryonic stem cells, including their ability to proliferate while retaining tissue-forming capabilities. The scientists have also shown that these epigenetic changes are fully reversible upon the dissociation of CTC clusters.
In their search for a substance that suppresses metastasis development, the research team tested 2486 FDA-approved compounds used for a number of different indications. They found inhibitors with the unexpected ability to dissociate patient-derived CTC clusters. This drug-based dissociation of CTC clusters into individual cells also resulted into epigenetic remodeling and prevented the formation of new metastases.
Preventing metastasis versus killing cancer cells
”We thought of acting differently from standard approaches, and sought to identify drugs that do not kill cancer cells, but simply dissociate them,” states Nicola Aceto, holder of an ERC starting grant and SNSF professorship.
In the fight against breast cancer, metastases remain the greatest danger. These new findings on the mechanisms of metastasis formation are the result of a large collaborative effort across various disciplines. “Our ambitious approach would not have been possible without collaboration with outstanding clinicians, molecular and computational biologists, with the support of state-of-the-art technology platforms,” says Aceto and adds: “Our methodology is positioned directly at the interface between these different disciplines. We are already working on the next step, which is to conduct a clinical trial with breast cancer patients.”
The accompanying image was chosen as cover story for the current issue of "Cell". A workshop report on the production of the picture is available under this link once the embargo has expired: https://medium.com/sci-five-university-of-basel
Prof. Dr. Nicola Aceto, University of Basel and University Hospital Basel, Department of Biomedicine, phone: +41 61 207 0773, email: Nicola.Aceto@unibas.ch
Sofia Gkountela, Francesc Castro-Giner, Barbara Maria Szczerba, Marcus Vetter, Julia Landin, Ramona Scherrer, Ilona Krol, Manuel C. Scheidmann, Christian Beisel, Christian U. Stirnimann, Christian Kurzeder, Viola Heinzelmann-Schwarz, Christoph Rochlitz, Walter Paul Weber, Nicola Aceto
Circulating Tumor Cell Clustering Shapes DNA Methylation to Enable Metastasis Seeding
Cell (2018), doi: 10.1016/j.cell.2018.11.046
Iris Mickein | Universität Basel
Airborne chemicals instantly identified using new technology developed at NTU Singapore
16.10.2019 | Nanyang Technological University
Family of crop viruses revealed at high resolution for the first time
15.10.2019 | John Innes Centre
A very special kind of light is emitted by tungsten diselenide layers. The reason for this has been unclear. Now an explanation has been found at TU Wien (Vienna)
It is an exotic phenomenon that nobody was able to explain for years: when energy is supplied to a thin layer of the material tungsten diselenide, it begins to...
Researchers at Ludwig-Maximilians-Universitaet (LMU) in Munich have explored the initial consequences of the interaction of light with molecules on the surface of nanoscopic aerosols.
The nanocosmos is constantly in motion. All natural processes are ultimately determined by the interplay between radiation and matter. Light strikes particles...
Particles that are mere nanometers in size are at the forefront of scientific research today. They come in many different shapes: rods, spheres, cubes, vesicles, S-shaped worms and even donut-like rings. What makes them worthy of scientific study is that, being so tiny, they exhibit quantum mechanical properties not possible with larger objects.
Researchers at the Center for Nanoscale Materials (CNM), a U.S. Department of Energy (DOE) Office of Science User Facility located at DOE's Argonne National...
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...
02.10.2019 | Event News
02.10.2019 | Event News
19.09.2019 | Event News
16.10.2019 | Physics and Astronomy
16.10.2019 | Life Sciences
16.10.2019 | Physics and Astronomy