Mapping Metastasis: Scientists Discover how Cancer Cells Colonize Distant Organs

How does cancer spread? How does it traverse from one organ to the next—often undetected—until it has colonized the far reaches of the human body? And more importantly, how can researchers stop this from happening?

These questions plague even the most renowned experts, but new research from scientists at Brown University has uncovered clues to cancers’ unique ability to invade our bodies—offering important insight into how we might develop tools to stop this disease’s most dangerous ability.

Cancer cells advance across a microchip designed to be an obstacle course for cells. The device sheds new light on how cancer cells invade and could be used to test drugs aimed at preventing cancer spread. [Credit: Ian Y. Wong / Brown University]

Cancer cells advance across a microchip designed to be an obstacle course for cells. The device sheds new light on how cancer cells invade and could be used to test drugs aimed at preventing cancer spread. [Credit: Ian Y. Wong / Brown University]

Reporting in this week’s issue of Nature Materials, biomedical engineer Dr. Ian Wong and his team devised a special microchip technology that tracks individual cancer cells as they navigate from one end of the chip to the other. Importantly, this tool uncovered how cancer cells hijack an otherwise normal cellular process to infect the body.

This process, called the epithelial-mesenchymal transition (or ‘EMT’) normally occurs in the developing embryo, when one type of cells, called epithelial cells, transforms into mesenchymal cells. Epithelial cells tend to clump together into larger groups, whereas mesenchymal cells can more easily and more quickly break away from the pack and travel individually. This transition is crucial to embryonic development, as it allows for cells to get to where they need to be at the appropriate time.

However, scientists have recently begun to hypothesize that cancer uses EMT as a tool to help it metastasize—traversing throughout the body and setting up shop in various tissues and organs. Metastasis is one of the biggest hurdles to eradicating cancer, and is responsible for 90% of all cancer-related deaths.

As Wong explained in yesterday’s news release:

“People are really interested in how EMT works and how it might be associated with tumor spread, but nobody has been able to see how it happens. We’ve been able to image these cells in a biomimetic system and carefully measure how they move.”

The research team used microchip technology to essentially build a microscopic ‘obstacle course,’ which cancer cells had to navigate. Made from a silicon wafer and tiny pillars just 10 micrometers in diameter and spaced so close together with just enough space for the cells to squeeze in between. Then, using fluorescent dye and time-lapse photography, they watched as the cells moved from one end of the chip to the other. According to Wong:

“We can track individual cells, and because the size and spacing of these pillars is highly controlled, we can start to do statistical analysis and categorize these cells as they move.”

This amazing video revealed that cells moved across the plate at two different speeds.

Most moved slowly, often clumping together, exhibiting classic epithelial cell behavior. But a minority of cells sped through the obstacle course individually—breaking away from the pack. These cells, Wong argues, have switched to mesenchymal cells after experiencing EMT.

“In the context of cell migration, EMT upgrades cancer cells from an economy model to a fast sports car. Our technology enabled us to track the motion of thousands of ‘cars’ simultaneously, revealing that…some sports cars break out of traffic and make their way aggressively to distant locations.”

These ‘breakaway’ cells are how cancer can reach, invade and, ultimately destroy, distant organs.

But this newfound knowledge also hints at a possible therapeutic strategy: developing a drug that reverses EMT in cancer cells, keeping them in clumps and slowing their progress.

“An interesting therapeutic strategy might be to develop drugs that downgrade mesenchymal ‘sports cars’ back to epithelial ‘economy models’ in order to keep them stuck in traffic, rather than aggressively invading surrounding tissues.’

Want to learn more about how cancer spreads? Check out our Solid Tumor Fact Sheet.

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