Researchers at the University of Basel have identified a cellular mechanism that sustains metastasis in highly aggressive cancers, offering a potential strategy to thwart the spread of disease. The new findings illuminate a pathway that could prevent the formation of secondary tumors, presenting a clear target for future therapies. The study appears in EMBO Magazine.
Metastasis describes the process by which cancer cells travel from the original tumor to distant parts of the body. This spread can occur through the bloodstream, the lymphatic system, or along body cavities, allowing cancer to seed new sites. In their investigation, the scientists focused on breast cancer, a disease known for its tendency to disseminate to organs such as the lungs and brain. By examining how those cancer cells behave in different environments, the team sought to understand what enables metastatic growth and colonization in new tissues.
A striking observation emerged: breast cancer cells often produce unusually high levels of the NNMT enzyme. This overproduction correlates with an increase in collagen synthesis within cancer cells. The excess collagen appears to create a microenvironment that is more permissive for cancer cells to anchor themselves in foreign tissues. In laboratory experiments, removing NNMT from aggressive breast cancer cells markedly reduced their ability to form metastases. When these NNMT-depleted cells were introduced into animal models, the resulting metastatic spread was dramatically diminished, and collagen production in those cells dropped as well. This suggests that NNMT acts as a driver of metastatic competence by modulating the extracellular matrix that supports colonization at distant sites.
The researchers stress that NNMT could be a viable target for therapeutic intervention. By disrupting NNMT activity, it may be possible to limit the metastatic capacity of cancer cells and slow the progression of disease. The team is already planning follow-up work to test existing NNMT inhibitors in mouse models and to monitor any potential side effects, aiming to translate these insights into safe and effective therapies for patients dealing with metastatic breast cancer and possibly other cancers where NNMT is implicated.
In the broader context of cancer research, the discovery adds to a growing body of evidence that metabolic enzymes can influence tumor spread beyond their traditional roles in energy production. By linking NNMT to collagen-rich changes in the tumor microenvironment, the study highlights how metabolic pathways intersect with the extracellular scaffolding that cancer cells exploit to invade new tissues. This integrated view of metabolism and matrix remodeling opens doors to combination strategies that pair NNMT inhibitors with other treatments, potentially enhancing the effectiveness of existing therapies in preventing metastasis. These insights contribute to a more nuanced understanding of how primary tumors communicate with distant organs and how disrupting this dialogue could alter disease trajectories.
Overall, the work from Basel underscores the importance of targeting the metastatic cascade as a complementary approach to controlling primary tumor growth. If further research confirms the safety and efficacy of NNMT blockers in humans, clinicians may gain a new tool to reduce metastasis risk, preserve organ function, and extend survival for patients facing aggressive breast cancer and related malignancies. The implications extend beyond a single cancer type, offering a framework for evaluating NNMT-related strategies across a range of tumors that rely on similar mechanisms to seed distant sites. (EMBO Magazine attribution)