Understanding Metastasis And How It Begins

Researchers have identified a cellular culprit that might help understanding how metastasis begins.
Researchers have identified a cellular culprit that might
help understanding how metastasis begins. (Image source)
Most cancer deaths occur because of metastasis, yet progress in preventing and treating migratory cancer cells has been slow. Researchers have now identified a cellular culprit that should help researchers better understand how metastasis begins. Their findings may also inform the design of new treatments to combat it.
As reported in Cell, the team discovered that an overabundance of a cell receptor called Frizzled-2, along with its activator, Wnt5, appears to raise a tumor's likelihood of metastasizing by triggering a process known as the epithelial-mesenchymal transition, or EMT.
EMT normally plays a role in human development, allowing certain cells to become mobile and invasive so they can move around and form new structures in the growing embryo. Previous studies have linked EMT to cancer metastasis, where tumor cells acquire those properties to disastrous effect.
After learning the importance of Frizzled-2, the researchers developed an antibody to block it. The antibody curbed metastasis in mice with certain types of tumors. The researchers are now pursuing further studies of the antibody with the hope that it can one day be turned into a metastasis-fighting drug.
The study also illuminates an important biological process and may contribute to better predictions of metastasis likelihood and patient survival.
Researchers had known that cell signaling pathways activated by the Wnt ("wint") protein family influence EMT, but they weren't sure how. The researchers examined various Wnt signals, and the Frizzled family of receptors they bind to, in many cancer cell lines. They found that Wnt5 and its receptor, Frizzled-2, were present at higher than normal levels in metastatic liver, breast, lung and colon cancer cell lines. In tissue samples from 48 cancer patients, Frizzled-2 was higher in late-stage cancers than in early-stage cancers. And patients with late-stage liver cancer who had high levels of Frizzled-2 had lower survival rates.
The team then painstakingly pieced together the players linking Wnt5 with the onset of metastatic behavior and discovered a previously unknown Wnt pathway. Frizzled-2, it turned out, could activate STAT3, which is known to drive cancer through EMT.
In addition to exploring Frizzled-2 as a new drug target, a potential biomarker for metastasis and a possible addition to the factors that predict patient survival, next steps include nailing down other pathway players to gain a full understanding of EMT in cancer and beyond.