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Scientists from the German Cancer Research Center (DKFZ) and Heidelberg University have made significant strides in understanding the behavior of spreading tumor cells at the site of metastasis. The study, conducted in mice, sheds light on the critical role of the epigenetic status of cancer cells in determining their fate upon reaching a distant organ. The findings, also validated in experiments with human tumor cells, could pave the way for novel diagnostic and therapeutic applications.
Metastasis, the process where cancer cells leave the primary tumor and establish daughter tumors in distant organs, poses a significant threat. While primary tumors can often be effectively treated, metastases are a leading cause of cancer-related deaths.
The research team developed a method to observe the behavior of migrating cancer cells in mice upon reaching the metastatic organ, in this case, the lung. They discovered that some tumor cells, upon arrival, exit the blood vessel and enter a resting state, while others start dividing within the blood vessel and grow into metastases. The decision between dormancy and immediate growth is influenced by endothelial cells lining the blood vessels, releasing factors from the Wnt signaling pathway that promote the exit of tumor cells and initiate latency.
The crucial discovery was that the epigenetic status of the cancer cells determined their fate. Tumor cells with less methylated DNA responded to Wnt factors, leading to latency, while more methylated cancer cells did not respond and immediately started metastatic growth. This subtle difference in DNA methylation was found to directly correlate with the metastatic potential of the tumor cells.
The study’s senior author, Hellmut Augustin, highlighted the potential implications of these findings for tumor diagnosis and therapy. Methylation patterns could be used as biomarkers to predict the likelihood of relapse after successful treatment of the primary tumor. Further studies are needed to validate these findings in natural human tumors.
The research represents a significant step forward in unraveling the complexities of metastasis and opens avenues for personalized approaches to cancer diagnosis and treatment.
