A better way to understand metastasis
THE most insidious thing about cancer is its tendency to spread. A lone primary tumour can be tackled by knife or radiation beam, as well as drugs, with a reasonable hope of success. But once it has metastasised, and spread secondary cancers around a patient’s body, such treatments are much less likely to be effective for any length of time. Stopping metastasis would thus be a great achievement. And a device created by Matteo Moretti of the Galeazzi Orthopaedic Institute, in Milan, and Roger Kamm of the Massachusetts Institute of Technology, may be a step towards that goal. Their invention, which they describe in Biomaterials, is a lab-on-a-chip that mimics the metastasis of breast cancer into bone marrow.
One of the mysteries of metastasis is why migrant cells from different sorts of primaries prefer to set up home in particular types of secondary tissue. To test their device the two researchers studied the well-established proclivity of breast-cancer cells (pictured above) to colonise bone. They wanted to look at the hypothesis that in this case the attraction is between a signalling molecule called CXCL5, which bone cells use to talk to other cells, and a molecular receptor called CXCR2, which is often found on the outer membranes of breast-cancer cells.
The chip itself is a glass and plastic sandwich 2cm across that contains a series of interlinked channels in the junction between the two materials. The channels are filled with a gel in which cells can grow. Dr Moretti, Dr Kamm and their students used these chips to create matrices of blood vessels, bone cells and stem cells which they hoped resembled the living marrow of a bone. They then placed clusters of breast-cancer cells in the middle of each chip. As a control, they did something similar using matrices of collagen (a protein abundant in bone) instead of ersatz marrow. As they guessed would happen, the cancer cells quickly invaded the marrow, but not the collagen. The question was, what was attracting them in?
To find out, they repeated the experiment with breast-cancer cells that had been incubated with antibodies to CXCR2. These glom onto the receptors and reduce their attraction to other substances. That slowed the cancer cells’ spread down a lot. Conversely, when they added CXCL5 to the collagen matrices, cancer cells moved in rapidly. The link between messenger and receptor thus seems to be what makes bone so attractive to breast-cancer cells.
This is useful information. Taking chemical aim at the CXCR2 receptor, or developing drugs that reduce the secretion by bone of CXCL5 might slow—or even halt—breast-cancer metastasis. But the new chips have wider ramifications, too. In making them Dr Moretti and Dr Kamm have created a way of testing many types of cellular interaction, including those between other cancers and the tissues they like to colonise. That may, eventually, result in less metastasis, fewer secondaries and longer lives for patients.
This article appeared in the Science & technology section of the print edition under the headline "Secondary goals"
From the February 15th 2014 edition
Discover stories from this section and more in the list of contentsExplore the edition
Analysis of a coin suggests there was, at least in his own eyes, an Emperor Sponsian
NASA’s rover has imaged what could be the remnant of an ancient river delta
They offer ways to produce cement without releasing carbon dioxide