Elizabeth Comen, MD

Understanding how nerves regulate and promote breast cancer metastasis.

Impact

Cancer cells create a complex environment around themselves, the tumor microenvironment, that helps them grow and spread to other parts of the body. Recent research has shown that cells lining blood vessels (endothelial cells) and immune cells in this environment play a significant role in promoting the spread of breast cancer. It was previously believed that more blood vessels around tumors simply supplied them with more oxygen and nutrients, aiding their growth. Now, it has been discovered that these blood vessels also send signals that actively encourage cancer cells to spread to new locations. Nerves in tumors were previously thought to be passive, simply providing routes for cancer cells to move along. Recently, studies have shown that nerves can help initiate tumors in some cancers. More innervation in these tumors is linked to higher chances of recurrence and poorer survival rates. It is not fully understood, however, how neurons regulate metastasis and how innervation changes as tumors become metastatic. Drs. Comen and Tavazoie are working toward understanding this connection.

Progress Thus Far

Drs. Comen and Tavazoie have discovered that breast tumors are frequently innervated by sensory nerves and that the amount of nerve input correlates with how likely the cancer is to spread. Using both patient data and a breast cancer model, they showed that sensory nerves actively support tumor growth and metastasis. When the team removed tumor innervating sensory nerves using a targeted approach, tumor growth slowed, and lung metastases were significantly reduced. They also developed a new co-culture system showing that sensory neurons help cancer cells grow and spread—even without direct contact—through the release of a still-unknown molecule. These findings reveal a new and important role for nerves in breast cancer and suggest that blocking this communication could be a new strategy to prevent metastasis.

What’s next

Drs. Comen and Tavazoie aim to identify the molecule released by sensory nerves that helps breast cancer cells grow and test its role in metastasis. The team will determine the cancer cell receptor through which this molecule signals. They will also study when in metastatic progression nerves have the greatest impact—during tumor growth, invasion, or spread—and whether immune cells are involved. Finally, Drs. Comen and Tavazoie will investigate whether and how signals from blood vessels help guide nerves into tumors.