New Imaging Tool Captures Process That Turns Tumor Cells Malignant in Breast Cancer

A new imaging technique that visualizes individual cells with high resolution may improve the understanding of key events in breast cancer development, including how and when cells turn invasive and spread elsewhere.

The tool, which already has helped explain mechanisms used by cancer cells to evade treatment, was described in the study, “Intraclonal Plasticity in Mammary Tumors Revealed through Large-Scale Single-Cell Resolution 3D Imaging,” published in Cancer Cell.

Like other types of cancer, breast tumors are known to be highly heterogeneous, which can diminish treatment effectiveness. However, the way cancer cells interact with each other and acquire different characteristics throughout tumor development is still poorly understood.

“A comprehensive view of tissue composition, cell shape, cell-cell interactions, and cell-fate decisions in complex biological specimens requires sophisticated 3D imaging and longitudinal imaging technologies,” the investigators wrote.

Scientists at the Walter and Eliza Hall Institute of Medical Research in Australia described a new 3D imaging method that allows them to visualize mammary tumors at the single-cell scale. With this technique, they set out to investigate how tumor cells develop from pre-cancerous cells in the mammary ducts, and continue to change their characteristics and behavior.

Using two different mouse models of breast cancer, researchers calculated exactly how many malignant cells developed from pre-cancerous cells in the mammary gland of female mice.

This process is quite complex and involves several steps, including the transformation of pre-cancerous cells into early stage cancer cells, which may then acquire different characteristics and become malignant, and capable of spreading to other organs or tissue.

Findings using this technique showed that only a small percentage of pre-cancerous cells from the mammary gland actually give rise to malignant breast cancer cells. But once the process is complete, these cells become highly changeable and difficult to target and eliminate with standard cancer treatments.

According to researchers, this happens because malignant cancer cells go through a process called epithelial-to-mesenchymal transition (EMT), in which their genetic and molecular signatures are switched from those of an epithelial cell to those of a mesenchymal cell.

While epithelial cells — like those forming the skin — remain tightly attached to each other creating a barrier between different tissues, mesenchymal cells are highly motile and tend to invade other tissues. For this reason, once cancer cells go through EMT, they acquire mesenchymal characteristics and that make them more likely to become invasive and spread.

“If EMT frequently occurs in breast cancers, it means the cells are a ‘moving target’ — they can evade one set of weapons we have to fight the cancer, meaning we need to develop strategies that are more broadly targeted,” Geoffrey J. Lindeman, a study’s author, said in a news release.

Anne C. Rios, the study’s lead author now with the Princess Máxima Center for Pediatric Oncology, in The Netherlands, noted that being able to visualize the 3D structure of the tumors at the single-cell scale was a critical step to these discoveries.

“We developed a new, rapid way to prepare tissue samples that retains their intricate architecture but allows us to distinguish individual cells and the three-dimensional structure of the tissue,” she said. “Our method enabled us to capture previously unseen images of breast tissue and mammary tumors — this was crucial for us to discover the frequency of EMT within the tumors.”

The team now hopes their tool may be used to facilitate a diagnosis by allowing physicians to examine in great detail a tumor’s structure, as well as the presence of specific cancer biomarkers.