To metastasize and invade distant parts of the body, cancer cells need help. And researchers from the Massachusetts Institute of Technology (MIT) recently discovered that the Mena protein aids and abets cancer in metastasis
. The findings point to potential diagnostics and new targets for preventing the spread of cancer.
For cancer, survival rate is inversely correlated with metastasis, the spread of cancer from the primary site to secondary organs. In fact, about 90% of cancer deaths are attributed to metastatic events.
To spread, cancer cells must get to the blood vessels around the body. But under normal conditions, cells are supported by a extracellular matrix known as fibronectin. The tangled and complex nature of fibronectin makes it hard for cells to pass.
However, researchers found that cancer cells which express a rogue form of the normal Mena protein, distinguished as Mena invasive (MenaINV), can dramatically remodel the fibronectin landscape. In particular, MenaINV binds strongly to the alpha-5 integrin receptor, which causes fibronectin to untangle itself into long bundles. This action also stimulates collagen to be organized into stiff fibrils that makes a direct path from primary tumor source. From there, cancer cells have a clear passageway to travel toward the blood vessels.
The organization pattern of collagen and fibronectin as radial fibrils from a tumor mass typically indicate aggressive cancers. “If you have curly, coiled collagen, that's associated with a good outcome, but if it gets realigned into these really straight long fibers, that provides highways for these cells to migrate on," said Madeleine Oudin, postdoctoral fellow at the Koch Institute and first study author.
Studies in mice also confirmed the role of MenaINV in metastasis, seen in the left image. In this image of a mouse tumor, cancer cells (green) remodeled the structure of their surrounding so that collagen fibers (blue) are now straightned and easier to traverse to get to the blood vessels (red).
In studies of breast cancer patients, the researchers found a link between earlier deaths induced by metastasis, and high levels of MenaINV. The same trend might also hold true for other cancers, like lung and colon cancer, though additional study is pending.
As of now, the researchers are working to develop antibodies against MenaINV. Success in this area could translate to diagnostic tests to predict a cancer’s likelihood to spread and guide targeted therapies. In addition to detection, the results point researchers to MenaINV as a new target in the fight against cancer. Understanding weaknesses in MenaINV could lead to drugs that inhibit or cancel its effects, thereby halting the spread of cancer.
Additional source: EurekAlert!