Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Tumors backfire on chemotherapy

02.01.2019

Some patients with breast cancer receive chemotherapy before the tumor is removed with surgery. This approach, called 'neoadjuvant' therapy, helps to reduce the size of the tumor to facilitate breast-conserving surgery, and can even eradicate the tumor, leaving few or no cancerous cells for the surgeon to remove. In those cases, the patients are very likely to remain cancer-free for life after surgery.

But not all tumors shrink under chemotherapy. If the tumor resists neoadjuvant therapy, there can be a higher risk of developing metastatic disease, meaning that the tumor will recur in other organs, such as bones or lungs.


Endothelial cells (blue/grey) internalizing exosomes (red) released from chemotherapy-treated tumors.

Credit: C. Cianciaruso/I. Keklikoglou/EPFL

This could be due to cancerous cells that resist chemotherapy and spread to other organs while the primary tumor is being treated.

Now, an international team of scientists led by Michele De Palma at EPFL has shed new light into this process. Working with experimental tumor models, the researchers found that two chemotherapy drugs frequently used for patients, paclitaxel and doxorubicin, induce mammary tumors to release small vesicles called exosomes.

Under chemotherapy, the exosomes contain the protein annexin-A6, which is not present in the exosomes released from untreated tumors. "It seems that loading of annexin-A6 into exosomes is significantly enhanced in response to chemotherapy," explains Ioanna Keklikoglou, first author of the study.

After being released from a chemotherapy-treated tumor, the exosomes circulate in the blood. Upon reaching the lung, the exosomes release their content, including annexin-A6. This stimulates the lung cells to release another protein, CCL2, which attracts immune cells called monocytes.

This immune reaction can be dangerous, as previous studies have shown that monocytes can facilitate the survival and growth of cancerous cells in the lung, which is one of the initial steps in metastasis. "In short, our study has identified a new link between chemotherapy and breast cancer metastasis," says De Palma.

Corroborating their laboratory data, the researchers found increased levels of annexin-A6 also in the exosomes of breast cancer patients undergoing neoadjuvant chemotherapy. However, De Palma cautions against jumping to conclusions: "While this observation supports the significance of our findings, at the moment we don't know if annexin-A6 has any pro-metastatic activity in human breast cancer".

Importantly, the researchers found that neutralizing annexin-A6 or blocking monocytes during chemotherapy prevents the experimental mammary tumors from metastasizing to the lung. These results may help to improve the efficacy and safety of neoadjuvant chemotherapy.

"Various monocyte inhibitors have been developed for clinical use, so they may be tested in combination with neoadjuvant chemotherapy to potentially limit unwanted side effects mediated by exosomes," says De Palma.

"Our findings must not discourage patients from receiving neoadjuvant chemotherapy when it's indicated," adds the study's clinical team. "It remains an essential and potentially curative treatment for many invasive breast cancers, as shown by multiple clinical trials."

Professor De Palma' lab is part of the Swiss Institute for Experimental Cancer Research (ISREC) within the School of Life Sciences at EPFL. ISREC is deeply involved in the Swiss Cancer Center Léman (SCCL), a cancer research consortium that includes the University hospital of Lausanne (CHUV), the Geneva University Hospitals (HUG), the universities of Lausanne (UNIL) and Geneva (UNIGE), and EPFL.

Other contributors

  • The University of Edinburgh (MRC Centre for Reproductive Health)
  • Harvard Medical School (Massachusetts General Hospital Cancer Center and Department of Radiation Oncology)
  • University of Sheffield (Medical School)
  • Oregon Health & Science University (Department of Cell, Developmental and Cancer Biology and Knight Cancer Institute)
  • University of Los Angeles (Jonsson Comprehensive Cancer Center)
  • Albert Einstein College of Medicine (Department of Developmental and Molecular Biology)

Reference

Ioanna Keklikoglou, Chiara Cianciaruso, Esra Gu?ç, Mario Leonardo Squadrito, Laura M. Spring, Simon Tazzyman, Lore Lambein, Amanda Poissonnier, Gino B. Ferraro, Caroline Baer, Antonino Cassará, Alan Guichard, M. Luisa Iruela-Arispe, Claire E. Lewis, Lisa M. Coussens, Aditya Bardia, Rakesh K. Jain, Jeffrey W. Pollard, Michele De Palma. Chemotherapy elicits pro-metastatic extracellular vesicles in breast cancer models. Nature Cell Biology, 31 December 2018. DOI: 10.1038/s41556-018-0256-3

Media Contact

Nik Papageorgiou
n.papageorgiou@epfl.ch
41-216-932-105

 @EPFL_en

http://www.epfl.ch/index.en.html 

Nik Papageorgiou | EurekAlert!
Further information:
http://dx.doi.org/10.1038/s41556-018-0256-3

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Researchers watch quantum knots untie

After first reporting the existence of quantum knots, Aalto University & Amherst College researchers now report how the knots behave

A quantum gas can be tied into knots using magnetic fields. Our researchers were the first to produce these knots as part of a collaboration between Aalto...

Im Focus: A cavity leads to a strong interaction between light and matter

Researchers have succeeded in creating an efficient quantum-mechanical light-matter interface using a microscopic cavity. Within this cavity, a single photon is emitted and absorbed up to 10 times by an artificial atom. This opens up new prospects for quantum technology, report physicists at the University of Basel and Ruhr-University Bochum in the journal Nature.

Quantum physics describes photons as light particles. Achieving an interaction between a single photon and a single atom is a huge challenge due to the tiny...

Im Focus: Solving the mystery of quantum light in thin layers

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...

Im Focus: An ultrafast glimpse of the photochemistry of the atmosphere

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...

Im Focus: Shaping nanoparticles for improved quantum information technology

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...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

International Symposium on Functional Materials for Electrolysis, Fuel Cells and Metal-Air Batteries

02.10.2019 | Event News

NEXUS 2020: Relationships Between Architecture and Mathematics

02.10.2019 | Event News

Optical Technologies: International Symposium „Future Optics“ in Hannover

19.09.2019 | Event News

 
Latest News

Composite metal foam outperforms aluminum for use in aircraft wings

23.10.2019 | Materials Sciences

Researchers watch quantum knots untie

23.10.2019 | Physics and Astronomy

A technology to transform 2D planes into 3D soft and flexible structures

23.10.2019 | Medical Engineering

VideoLinks
Science & Research
Overview of more VideoLinks >>>