New Technique Predicts Aggressive Tumors Before They Metastasize

A team of researchers from The Institute of Cancer Research London (London, UK) and Barts Cancer Institute at Queen Mary University of London (BCI-QMUL, London, UK) explored how cancer cells use the arrangement of the ECM as a guide to leave the tumor. They found that the ECM triggers changes inside the cancer cells, altering their shape and enhancing their ability to move to other parts of the body. This breakthrough means that tumors likely to metastasize can now be identified earlier, enabling doctors to tailor treatments sooner. Drugs targeting the ECM’s structure, as well as the genes responsible for these shape changes, are currently in development, offering the potential to stop cancer before it can spread.

For their study, the research team examined tumor tissue from 99 patients with melanoma and breast cancer. They observed that the ECM was arranged differently in three distinct regions of the tumor. Like scaffolding, the ECM contains various components, including pole-like fibers. In the tumor’s core, the fibers were spread out and disorganized, while at the edges, they were tightly packed and thicker. At the outermost edge of the tumor, the fibers were oriented outward, providing a ‘pathway’ for cancer cells to escape. In this outer region, the cancer cells were rounded, a shape associated with increased invasiveness.

The team tested whether the conditions at the tumor’s border contributed to the aggressiveness of the cancer cells. They grew melanoma cells in a model that mimicked these conditions and injected them into mice. Cells grown under these conditions were more likely to spread to the lungs and metastasize compared to cells grown in control conditions with disorganized ECM fibers. The researchers also found that cells from the tumor’s outer edge had distinct gene profiles. These cells expressed more genes related to cell migration, cell rounding, and inflammation—traits that make the cells more aggressive and better equipped to survive. Furthermore, the team observed an increase in genes for enzymes that affect the organization of the ECM, highlighting how cancer cells manipulate their environment to facilitate tumor escape.

When the researchers compared their findings to cancers from patients with 14 different tumor types, including melanoma, breast, pancreatic, lung cancer, and glioblastoma—a highly aggressive brain cancer—they discovered that a higher presence of these genes was linked to a shorter survival time. Published in Nature Communications, these results suggest new treatment possibilities to address cancer before it spreads. One promising avenue is targeting lysyl oxidase (LOX) enzymes, which stabilize the ECM and are more prevalent at the tumor’s border. Drugs targeting LOX are already undergoing clinical trials for other medical conditions, offering hope for potential use in cancer treatment.

“Our research has uncovered the roadmap that cancer cells follow to break out of a tumor, enabling it to cause a secondary tumor elsewhere in the body," said Professor Victoria Sanz Moreno, Professor of Cancer Cell and Metastasis Biology at The Institute of Cancer Research. “Now that we understand this roadmap, we can look to target different aspects of it, to stop aggressive cancers from spreading.”