Squashing cancer cells makes them migrateS

When left untreated, cancer cells begin migrating away from the tumor where they first developed, spreading throughout the body and becoming much deadlier. But what stimulates this migration? A new study suggests that physical cell compression – which occurs when a tumor grows in certain parts of the body, where there is limited room and the cancerous cells get squashed together – could be one of the impetuses for cancer migration.

In the early stages of cancer, cells stick around the location where they originated, a step referred to as in situ. The tumors become more dangerous when they move on to the invasive stage, growing into cell layers beyond their first location. From the invasive stage , cancer can metastasize and spread throughout the body, becoming even more deadly. "Most people who die of cancer," states the National Cancer Institute website, "die of metastatic disease."

In order to limit cancer's spread, it is important that we understand how it grows and why it changes from in situ to invasive and invasive to metastatic. This new American paper examined in situ cells under pressure, specifically, their behavior when they were compressed.

Researchers used a heavy piston to squash cancerous epithelial cells, which make up certain glands and line body cavities, against a membrane. In addition, they applied the same pressure to normal epithelial cells as a control. While maintaining the pressure on the cells, the researchers scratched some cells away from the membrane and looked at how quickly new cells migrated into the gap. In the cancer cells, the constant pressure from the piston acted as a stimulus for migration, as the cells at the edge of the scratch wound stretched out filopodia, or cellular "antennae," which are a key characteristic of many different types of migrating cells.

The filopodia-wielding cells on the edge of the wound acted as "leader cells" for the others, stimulating them to migrate more quickly than the non-cancerous control cells as the leader cells "guided" them into the cell-free scratch. The cancer cells also became clingier, bonding more firmly to the membrane. The increased migration and the enhanced ability to hold on to healthy tissues would both make the compressed tumor more deadly had it been in a real human body. In a similar scratch where the cells were not compressed, on the other hand, fewer cells on the edge of the scratch transformed into leader cells.

In a real tumor, the compression that cancer cells experience comes from growing in a confined area. The researchers suggest the cancer treatment take this pressure into account when attempting to prevent tumors from becoming more invasive:

"The concept of mechanical induction of tumor invasiveness could open the door to a unique class of targets for blocking mechanical stress pathways and guide the development of approaches for drug screening that take into account mechanical as well as genetic biological factors."

Via PNAS