The Key to Unlocking Metastasis

Researchers at Emory University have found tiny finger-like projections are the driving force behind the invasive behavior in a rare subset of lung cancer cells.

 

Understanding how these filopodia within a tumor perform could be vital in unlocking metastasis – how cancer spreads to other parts of the body.

 

Cancer cells spread – metastasize – by moving into healthy tissue, lymph nodes, or organs. When cancer spreads to distant parts of the body, it is called metastatic cancer. (For many types of cancer, this is Stage IV cancer.)

 

Learning more about how cancer metastasizes is essential. A 2019 study determined that 66.7% of cancer deaths in solid tumors were caused by metastasis. (1)

 

The Emory scientists report that an invasive pack of cells has specialized roles as leaders and followers. The cells depend on each other for mobility and survival. The findings could help researchers develop treatments that prevent cancer from spreading by understanding the rare cells within a tumor necessary for deadly metastasis. (2)

 

Adam Marcus, a medical oncology professor at Emory, notes the epigenetic changes that distinguish leader cells and invasive behavior may appear in several types of cancer.

 

Having longer filopodia is linked with a gene called MYO10, which was the most up-regulated and abnormal in leader cells, compared with follower cells. Research points to both long filopodia and invasive behavior depend on MYO10 activity.

 

“We’re finding that leader and follower cells have a symbiotic relationship and depend on each for survival and invasion,” Marcus says. “Because metastatic invasion is the deadliest aspect of cancer, our goal is to find agents that disrupt that symbiotic relationship.

 

“It was known that MYO10 was linked to invasion and metastasis, but this is the first evidence that it is playing this specific role in a rare subset of cells,” he adds. “This could help us look for these rare cells in patient tumors to gauge how potentially invasive they are.”

 

Leader cells also secrete a sticky extracellular protein called fibronectin. The MYO10 protein helps filopodia rearrange fibronectin (a cell adhesion molecule) into fibrils.

 

Marcus and graduate student Jessica Konen, Ph.D., observed a mass of lung cancer cells embedded in a 3-D protein gel. While the cells generally stick together, occasionally a few cells extend from the mass, like tentacles.

 

“We saw that when the leader cell became detached or died unexpectedly, the followers could no longer move,” Konen says. “In one particular movie, we saw a leader cell come out away from the rest of the cells, and then seem to realize that nobody was following him. He actually did a 180, and went back to grab cells to bring with him.”

 

 

Citations

 

(1) Are 90% of deaths from cancer caused by metastases? https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6745820/

(2) Image-guided genomics of phenotypically heterogeneous populations reveals vascular signaling during symbiotic collective cancer invasion. https://www.nature.com/articles/ncomms15078