Squeezing Cancer Cells Offers New Insight into Metastasis

Researchers from the University of New South Wales recently reported that the squeezing of cancer cells by extremely narrow blood vessels may trigger these cells to become more capable of spreading throughout the body, offering fresh perspectives on metastasis.

To investigate, the team built a device simulating blood flow through channels narrower than 10 micrometres, mimicking the size of the smallest capillaries present in the human body. The device was fabricated using polydimethylsiloxane (PDMS), with channels decreasing from 30 down to just 5 micrometres in width. Human melanoma cells were pumped through these tiny channels at rates equivalent to natural blood flow. Within just 15 minutes, researchers observed that the cells physically deformed and exhibited increased levels of proteins linked to cancer spread and stem cell-like behavior. This suggests that squeezing triggers a reprogramming process, enabling these cells to survive, proliferate, and potentially form new tumors.

When mouse models lacking a functioning immune system were injected with the squeezed melanoma cells, the mice developed significantly more tumors in their lungs, bones, and brains compared to those that received unaltered cells. The study offered new evidence that physical stress from circulation may make cancer cells more aggressive and tumorigenic. Giulia Silvani, lead author of the study published in Nature Communications, emphasized the significance of recreating the journey of cancer cells in the laboratory. “Their journey through the body is so hidden, leaving little trace and making them incredibly difficult to capture in action. But we were able to recreate that journey in the lab, giving us a rare glimpse into the moment when these cells switch into their most aggressive state.

Senior author Kris Kilian highlighted that the findings suggest mechanical forces, not just rare cell types, are central to metastasis. “Our finding paints a new picture, where cancer cells are triggered into becoming more tumorigenic—meaning they can form new tumors—after squeezing through the narrowest of spaces, suggesting this process may precede events like bone and brain metastasis.”

These results could lay the groundwork for new prognostic and therapeutic strategies focused on the mechanical environment of cancer cells.