On the move; new device follows metastasis

Cancer researchers have got an unprecedented microscopic look at metastasis thanks to a new device which sheds light on how tumour cells travel.

Engineers at Johns Hopkins University invented a device which videoed an individual human breast cancer cell as it burrowed through a 3D collagen matrix resembling human body tissue – a process known as invasion.

"There's still so much we don't know about exactly how tumour cells migrate through the body, partly because, even using our best imaging technology, we haven't been able to see precisely how these individual cells move into blood vessels," said Andrew D. Wong, a doctoral student in the Department of Materials Science and Engineering. "Our new tool gives us a clearer, close-up look at this process."

Wong also recorded a single cancer cell working its way through the wall of an artificial blood vessel into the bloodstream before hitch a ride to other parts of the body to form new tumours – known as intravasion.

[caption id="attachment_40594" align="alignright" width="200"] Tiny tubes connected to the chip carry a fluid that behaves like the bloodstream, allowing the researchers to study how metastasis occurs. Credit: Will Kirk/Johns Hopkins University[/caption]

Wong replicated these processes in a small transparent chip incorporating both the artificial blood vessel and the surrounding tissue material. A nutrient-rich solution flows through the vessel, mimicking the properties of blood. Fluorescently-labelled breast cancer cells were inserted individually and in clusters in the tissue near the vessel, enabling their behaviour to be monitored via a microscopic viewing system.

This gives researchers a clearer view of the complex physical and biochemical interplay taking place when cells leave a tumour, move through the surrounding tissue and approach a blood vessel. It has already yielded detailed images of a cancer cell as it found a weak spot in the vessel wall, exerted pressure on it and squeezed through far enough so that the force of the passing current swept it into the circulating fluid.

"Cancer cells would have a tough time leaving the original tumour site if it weren't for their ability to enter our bloodstream and gain access to distant sites," Wong said. "So it's actually the entry of cancer cells into the bloodstream that allows the cancer to spread very quickly."

This work has been published in Cancer Research. Researchers now hope to use the device to test various cancer-fighting drugs to get a better look at how the medications perform and how they might be improved.

Breast cancer cell invades artificial blood vessel

Live-cell imaging of invasion and intravasation in an artificial microvessel platform