NIH Scientists Find Pathway to Regulate Cancer Growth and Metastasis in Mice

In a mouse study published this month in the Journal of Clinical Investigation, scientists from the National Institute of Environmental Health Sciences (NIEHS) present a novel way to prevent tumor metastasis by eliminating the blood vessels that feed the tumor. If the production of small molecules known as epoxyeicosatrienoic acids (EETs) is stopped, cancer cells do not get the oxygen and nutrients that they need to grow.

EETs regulate inflammation and vascular tone, and drugs that raise EETs are being investigated in clinical trials for many diseases such as hypertension and diabetes. However, previous work has demonstrated that EETs make tumor cells grow faster and cause them to migrate. Dr. Darryl Zeldin and colleagues explored this finding by creating two mice strains – one with high levels of EETs and one with low levels of EETs. The mice with higher EETs developed more metastatic tumors compared to the mice with lower EETs. EETs produced by the tumor itself as well as by surrounding tissues stimulated tumor growth and migration. EEZE are EET antagonists that interfere with the pathway in mice and suppressed tumor growth and metastasis.

This research is the first to show that EETs work with vascular endothelial growth factor (VEGF) and are critical for tumor growth and metastasis. According to Dr. Mark Kieran, another author of the study, “The identification of an old pathway studied for many years in cardiovascular disease has found a new role in regulating cancer growth and metastasis, the primary causes of cancer-related deaths. With these findings, opportunities to better understand the underlying mechanisms that drive cancer, and thus the development of effective therapies for their treatment, moves one step closer to a reality.”

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