New imaging technology reveals the plasticity of breast cancer

  Researchers at Walter and the Eliza Hall Institute of Medical Research have developed a new imaging technique that can see key steps in the evolution of cancer cells within tumors, which may reveal how breast cancer evades treatment. Using laboratory models of breast cancer, researchers can observe tumors in three dimensions at a high resolution previously unattainable. This reveals how cancer cells develop from precancerous cells in breast ducts and the changes that occur in tumors over time.

  This study recently published in the journal Cancer Cell shows that breast cancer cells are inherently variable, changing from one cell type to another, similar to cells that spread more easily at the molecular level. The transformation of normal breast cells into cancer cells has gone through many stages. "Precancerous" cells evolve into early cancer cells, and then the cancer cells may change, making the cells more likely to spread from the tumor. So far, it has not been possible to see a single clone in the entire tumor-a "sister" cell derived from a single precancerous cell.

  The new imaging technology allows the research team to examine how often pre-breast cancer cells develop into tumors and observe the behavior of tumor cells. The research was led by Dr. Anne Rios, Professor Jane Visvader, and Professor Geoff Lindeman from the Walter and Eliza Hall Institute. Professor Visvader said: "Using a new imaging technique, we found that only a small percentage of precancerous cells will develop into tumors. On the contrary, once a tumor is formed, we found that its cells are likely to undergo the so-called'epithelial-mesenchymal transition'. (EMT). This is a change in the "molecular landscape"-genes in cells are turned on or off, changing them from the "epithelial" form to the "mesenchymal" form, which has a growth advantage. Our model shows EMT is not a rare event, but an inherent feature of breast tumor cells."

  These results come from a laboratory model similar to human breast cancer, so the research team suspects that human breast cancer may also show a high proportion of molecular EMT.

  Professor Lindeman said: "If EMT often occurs in breast cancer, it means that cells are a'moving target'-they can evade our series of weapons against cancer, which means we need to develop a broader targeting strategy. Dr. Rios said that a new three-dimensional imaging technology is critical to these findings.

  Dr. Rios said: "Up to now, it has been a challenge to observe the complex structure of complex tissues (such as breast tissue), or to observe the true arrangement of tumor cells. We have developed a new method for rapid preparation of tissue samples. The method preserves the complex structure of the tissue sample, but allows us to distinguish the three-dimensional structure of individual cells and tissues. Our method allows us to capture images of breast tissue and breast tumors that have never been seen before, which is useful for us to find EMT within tumors The frequency is crucial."

  Dr. Rios said: "We expect that our new imaging method will have many other applications in the study of normal and cancerous tissue samples."