Novel insight into metastasis could offer new treatments
Researchers from the United Kingdom may have made a breakthrough in cancer treatment, after discovering an unusual mechanism by which cancer cells spread and survive in the body.
In a study published in Nature Communications, researchers reveal how two molecules join forces to help cancer cells survive as they metastasize.
Researchers have uncovered a new mechanism by which cancer cells break away from tumors and spread to other parts of the body.
Metastasis is the process by which cancer cells break away from the primary tumor and spread to other parts of the body through the bloodstream or lymph system.
Once cancer has spread, the disease becomes much more challenging to treat.Chemotherapy, hormone therapy,radiotherapy, and other treatments can yield success for some metastatic cancers, but for most, the prognosis is poor.
As an example, the 5-year relative survival rate for women with localized breast cancer — cancer that has not metastasized — is 61 percent. This falls to just 6 percent for women whose breast cancer has spread to other parts of the body, such as nearby lymph nodes, the lungs, or bones.
As such, researchers are working hard to find ways to prevent cancer from spreading in the first place — and this latest study shows promise for a treatment that does just that.
New defense signaling process within cancer cells discovered
Lead researchers Dr. Stéphanie Kermorgant, of the Barts Cancer Institute at Queen Mary University London (QMUL), and colleagues set out to see what happens when cancer cells break away from tumors in cell cultures, zebrafish, and mice.
They found that “integrins” — proteins on the surface of a cell that bind and communicate with its surroundings — play an important role in the survival of cancer cells after they detach from a primary tumor.
The team explains that integrins are known to engage in “outside-in” and “inside-out” signaling, which helps cancer cells bind to their surrounding environment.
However, they found that when cancer cells travel during metastasis, the integrins adopt “inside-in” signaling, in which a form of defense signaling occurs within the cell.
The integrin beta-1 (β1) teams up with a protein called c-Met, and both proteins travel together inside the cancer cell, the authors explain.
The proteins then move to a location within the cell that is normally used for degradation and recycling of cell material. However, the proteins use this location to send a signal to other areas of the cancer cell, triggering a defense against cell death.
The researchers say this is the first time such a process has been identified in cancer metastasis.
Stopping β1 from entering cancer cells could prevent metastasis
Next, the team set out to see what would happen if both β1 and c-Met were prevented from entering cells or from traveling to the location needed for defense signaling.
On testing both strategies on breast and lung cells, they found that the cells were much less likely to metastasize, suggesting that β1 and c-Met play a vital role in cancer progression.
Dr. Kermorgant and colleagues believe their findings suggest that stopping β1 from initially entering cancer cells could be an effective way to combat cancer metastasis.
While integrin inhibitors are already being tested as cancer treatments, at present, such drugs target integrin signaling activity on the surface of cancer cells. The team says this may explain why these medications have yielded poor results.
“Metastasis is currently incurable and remains one of the key targets of cancer research. Our research advances the knowledge of how two key molecules communicate and work together to help cancer cells survive during metastasis.
We’re hoping that this might lead to the discovery of new drugs to block the spread of cancer within the body.” — Dr. Stéphanie Kermorgant
Credit: Honor Whiteman, http://www.medicalnewstoday.com/articles/311191.php