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

More articles from Life Sciences:

nachricht New technique to determine protein structures may solve biomedical puzzles
11.12.2019 | Dana-Farber Cancer Institute

nachricht NTU Singapore scientists convert plastics into useful chemicals using su
11.12.2019 | Nanyang Technological University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Highly charged ion paves the way towards new physics

In a joint experimental and theoretical work performed at the Heidelberg Max Planck Institute for Nuclear Physics, an international team of physicists detected for the first time an orbital crossing in the highly charged ion Pr⁹⁺. Optical spectra were recorded employing an electron beam ion trap and analysed with the aid of atomic structure calculations. A proposed nHz-wide transition has been identified and its energy was determined with high precision. Theory predicts a very high sensitivity to new physics and extremely low susceptibility to external perturbations for this “clock line” making it a unique candidate for proposed precision studies.

Laser spectroscopy of neutral atoms and singly charged ions has reached astonishing precision by merit of a chain of technological advances during the past...

Im Focus: Ultrafast stimulated emission microscopy of single nanocrystals in Science

The ability to investigate the dynamics of single particle at the nano-scale and femtosecond level remained an unfathomed dream for years. It was not until the dawn of the 21st century that nanotechnology and femtoscience gradually merged together and the first ultrafast microscopy of individual quantum dots (QDs) and molecules was accomplished.

Ultrafast microscopy studies entirely rely on detecting nanoparticles or single molecules with luminescence techniques, which require efficient emitters to...

Im Focus: How to induce magnetism in graphene

Graphene, a two-dimensional structure made of carbon, is a material with excellent mechanical, electronic and optical properties. However, it did not seem suitable for magnetic applications. Together with international partners, Empa researchers have now succeeded in synthesizing a unique nanographene predicted in the 1970s, which conclusively demonstrates that carbon in very specific forms has magnetic properties that could permit future spintronic applications. The results have just been published in the renowned journal Nature Nanotechnology.

Depending on the shape and orientation of their edges, graphene nanostructures (also known as nanographenes) can have very different properties – for example,...

Im Focus: Electronic map reveals 'rules of the road' in superconductor

Band structure map exposes iron selenide's enigmatic electronic signature

Using a clever technique that causes unruly crystals of iron selenide to snap into alignment, Rice University physicists have drawn a detailed map that reveals...

Im Focus: Developing a digital twin

University of Texas and MIT researchers create virtual UAVs that can predict vehicle health, enable autonomous decision-making

In the not too distant future, we can expect to see our skies filled with unmanned aerial vehicles (UAVs) delivering packages, maybe even people, from location...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

The Future of Work

03.12.2019 | Event News

First International Conference on Agrophotovoltaics in August 2020

15.11.2019 | Event News

Laser Symposium on Electromobility in Aachen: trends for the mobility revolution

15.11.2019 | Event News

 
Latest News

Self-driving microrobots

11.12.2019 | Materials Sciences

Innovation boost for “learning factory”: European research project “SemI40” generates path-breaking findings

11.12.2019 | Information Technology

Molecular milk mayonnaise: How mouthfeel and microscopic properties are related in mayonnaise

11.12.2019 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>