Chemokines are signals in the body that act as beacons, calling out to migrating cells, such as white blood cells, guiding them to where they are needed. One chemokine in particular, chemokine 25 (CCL25), binds to chemokine Receptor 9 (CCR9), forming a signaling pathway that is important in the small intestine and colon, where it regulates immune response and decreases cell death.
Drs. Steven Lipkin, Xiling Shen, and colleagues at Cornell University have discovered that the CCL25-CCR9 pathway also has an unexpected role— inhibiting colon cancer metastasis and invasion.
They found that CCR9 was highly abundant in early stage colon cancer cells derived from human cancer but surprisingly lacking in invasive and metastatic cancer, suggesting a role for this receptor in reducing the spread of colon cancer.
By blocking this pathway in early stage cancer cells, they showed that tumor formation within the small intestine/colon of mice was inhibited, but metastasis and invasion were increased. Furthermore, they found that activation of a second pathway called NOTCH, known to stimulate metastasis and invasion, promotes the degradation of CCR9, thus inhibiting the actions of its binding partner CCL25.
This discovery sheds light on how colon cancer progresses and metastasizes.
TITLE: Chemokine 25-induced signaling suppresses colon cancer invasion and metastasis