New Molecular Microscopy Tool Uncovers Breast Cancer Spread

Breast cancer commonly starts when cells start to grow uncontrollably, often due to mutations in the cells. Overtime the tumor becomes a patchwork of cells, called cancer clones, each with different mutations. As they are genetically different, they can have different reactions to treatments. For example, some of these cancer cells could become resistant to treatment, or some could spread around the body. The mutations that occur will be influenced by what is happening around the cancer, the cells that it is surrounded with, and the individual’s immune system. Therefore, being able to study the environment that a cancer cell is in, what mutations arise, and which cancer cells spread around the body gives a complete view of tumor evolution.

Now, a team of researchers from the Wellcome Sanger Institute (Cambridgeshire, UK) and collaborators has developed a new technology that can trace which populations of breast cancer cells are responsible for the spread of the disease, and for the first time highlights how the location of cancer cells could be as important as mutations in tumor growth. The new technology uses hundreds of thousands of tiny fluorescent molecular probes to interrogate cellular DNA and RNA and scan large pieces of tissue using fluorescence microscopy. It can genetically and physically map out a cancer's unique set of clones, how their gene expression programs change and show how they interact with their environment.

The team found that across multiple stages of breast cancer development there were specific, and often unexpected, patterns of clone growth and that genetic clones behave differently depending on where in the breast they started. The results also suggest that sometimes it is not only the genetics that influence how cancers grow, but also the location of the tumors. In this case, the genetics can be used as a tool to find out more about what happened in the situation that drove the cancer clones to spread around the body. In the future, it could be possible to develop therapies that could prevent or lessen the cancer’s ability to grow and spread, by influencing the environment around the tumor. In addition to this, researchers could use the newly developed tool to test how new treatments affect both the cancer and its interaction with the immune system, giving a complete picture of how therapies work and any possible side effects.

“We have created a system that combines computational and experimental techniques that allows us to map evolutionary cancer lineages in their natural habitat of human tissue,” said Artem Lomakin, first author from EMBL’s European Bioinformatics Institute (EMBL-EBI) and the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ). “While it has been previously possible to trace the lineage of cancer tumor cells in an experimental setup, this is the first time that multiple lineages were traced in human tissues, giving a complete overview of breast cancer development in the body. Insights generated by our system were impossible to get before, especially at this scale.”

“Our research has created a tool that can trace which breast cancer cells go on to cause tumors in other parts of the body, and can help answer some of the big questions in cancer, such as why some cancer cells spread and some don’t,” added Dr. Lucy Yates, co-senior author from the Wellcome Sanger Institute. “To fully understand and therefore treat breast cancer, we need to be able to see the entire picture of how the cancer interacts in the body, with the cells around it, and with the immune system. This new technology combines multiple techniques and expertise to do this, bringing together different approaches to give a complete view of cancer that has not been previously possible.”

Related Links:
Wellcome Sanger Institute