UM research makes groundbreaking discovery in study of breast cancer metastasis routes

MACAU, June 6 - A research team led by Chair Professor Chuxia Deng and Assistant Professor Miao Kai in the Faculty of Health Sciences (FHS) at the University of Macau (UM) has made a groundbreaking discovery in the study of cancer metastasis. The team, for the first time, conducted a qualitative and quantitative analysis of breast cancer metastasis routes by applying a barcoding system based on a single-cell lineage tracing approach (CellTag). The results revealed that cancer cells primarily disseminate via the lymphatic system rather than the bloodstream. The research also found that crosstalk between tumour cells and the tumour microenvironment (TME) determines the metastatic potential of cancer cells. The study systematically demonstrates tumour metastatic routes and opens up new avenues for the development of cancer treatment strategies. The research has been published in the prestigious journal Molecular Cancer.

Cancer metastasis is the primary cause of cancer-related death, yet the mechanisms that govern metastatic route selection remain elusive. Using CellTag technology, the research team tracked the dissemination of breast cancer cells in mouse models. They found that less than 3% of cancer cells spread through the bloodstream, while over 80% metastasised via the lymphatic system to distant organs, such as the lungs and liver. Further analysis showed that the lymph-disseminated cells have distinct gene expression patterns and communicate closely with stromal cells (such as fibroblasts and endothelial cells) in the microenvironment, forming a ‘seed-soil’ adaptive mechanism.

The study provides empirical evidence for route preference in cancer metastasis and demonstrates that tumour cells are ‘prewired’ with intrinsic information that determines their metastatic potential and organotropism. Additionally, these tumour cells dynamically adapt their gene expression based on the microenvironment of the target organs. These findings lays the foundation for the development of therapies targeting lymphatic metastasis, such as the inhibition of cytokine signalling or the disruption of tumour-stroma crosstalk to suppress metastasis.

Moreover, by using single-cell RNA sequencing technology, the research team found that genetically identical tumour cells exhibit organ-specific gene expression profiles. This further demonstrates the pivotal role of the microenvironment in shaping tumour cell behaviour. For example, lung metastatic cells upregulate oxidative stress-related genes, while liver metastatic cells activate metabolic regulatory pathways.

The study was led by the Cancer Centre of UM FHS, with Prof Deng and Prof Miao serving as the corresponding authors. The research was funded by the Science and Technology Development Fund of the Macao SAR (File No.: 0073/2021/A2, 111/2017/A, 0007/2021/AKP, 0009/2022/AKP, 0004/2021/AKP, and 0065/2022/A2), and UM (File No.: MYRG-GRG2023-00150-FHS-UMDF and MYRG-GRG2024-00146-FHS). The full version of the research article is available at: https://doi.org/10.1186/s12943-025-02279-w.