Scientists have found that the spread of cancer and the formation of fatal metastases are influenced by DNA methylation patterns and endothelial cell action, providing new insights into cancer** and patient prognosis. Credit: scitechdailycom
The study highlights the critical role of endothelial cells and DNA methylation in cancer metastasis, pointing to new diagnostic and ** strategies.
Scientists from the German Cancer Research Center (DKFZ) and the University of Heidelberg studied the behavior of spreading tumor cells at the site of metastasis in mice: some tumor cells immediately began to form metastases. Others leave the blood vessels and may then enter a long period of dormancy. What determines which path cancer cells go is their epigenetic state. This has also been confirmed in experiments with human tumor cells. The results of the study could pave the way for new diagnostics and applications.
What makes cancer so dangerous? Cancer cells that leave the primary tumor and reach distant parts of the body, where they may grow into daughter tumors, called metastases. While most primary tumors can be treated effectively**, metastasis is the real danger. Oncologists estimate that more than 90% of cancer deaths in solid tumors are due to metastasis.
For decades, researchers have been working to understand and prevent the spread of tumor cells. However, the mechanisms that enable cancer cells to survive in distant organs and eventually develop metastases remain largely unknown.
To spread throughout the body, cancer cells spread through the bloodstream and lymphatic system. Scientists at DKFZ and the University of Heidelberg have now developed a method to observe the behavior of mice migrating cancer cells as soon as they reach a metastatic organ, in this case, the lungs.
The research team, led by two first authors, Moritz Jakab and Ki Hong Lee, found that some tumor cells, once they reach the metastatic organ, leave the blood vessels and enter a resting state. Other cancer cells begin to grow directly within the blood vessels** and grow into metastases.
This delicate fate decision of metastatic tumor cells is controlled by the endothelial cells that line the inside of all blood vessels. They release factors from the Wnt signaling pathway, promoting tumor cells to exit from blood vessels, thereby initiating the incubation period. When the researchers turned off the Wnt factor, the delay no longer occurred.
At this point, we ask ourselves the question: Why do some cancer cells immediately metastasize, while others go into a state of sleep? Moritz Jakab said. There are no genetic differences between dormant and metastatic cancer cells, nor are there differences in many other molecules. But the researchers were able to detect a subtle difference: the methylation of DNA differed between the two cell types. Tumor cells with low levels of DNA methylation are sensitive to factor WNT responses, resulting in vascular extravasation and subsequent latency. On the other hand, cancer cells with a higher degree of methylation do not respond to the Wnt factor, remain in the blood vessels, and immediately begin metastatic growth.
To test this hypothesis, the team examined the DNA methylation status of various tumor cell lines. In fact, they found that it was directly related to their potential for transfer.
These results are surprising and could have far-reaching implications for tumor diagnosis and**. For example, the results of the study could help use certain methylation patterns as biomarkers to determine how high the burden of dormant cancer cells in patients is, and thus how likely the patient is to be after a successful primary tumor," said senior author Hellmut Augustin. "But first, we need to investigate whether natural human tumors behave the same as the cell lines or experimental tumors employed.
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