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by Alexander Gelfand
Researchers are discovering how the blood’s wound-healing platelets have a hand in metastasis as well.
Sometimes, it pays to revisit an old idea.
In the 1960s, scientists began to see evidence that platelets do more than gather around wounds to staunch bleeding and promote wound healing. These tiny fragments in the bloodstream appeared to also promote metastasis, the spread of cancer cells through the body, which is responsible for 90 percent of cancer deaths. But how?
Richard Hynes, an HHMI investigator at the Massachusetts Institute of Technology, is especially interested in cell adhesion—how cells stick to each other and to body tissues—and the ways it contributes to human disease. In experiments conducted nearly 10 years ago, Hynes and collaborators demonstrated that cell adhesion proteins known as selectins, located on the surface of platelets, are involved in metastasis.
At the time, the Hynes group was occupied with studying the role of cell adhesion in vascular development and screening for adhesion-related genes that enhance or suppress tumor metastasis. “No one had time to concentrate on the platelet question,” he says.
When postdoc Myriam Labelle joined the Hynes lab four years ago, she picked up the platelet thread—with illuminating results. In a series of experiments published November 15, 2011, in Cancer Cell, the team revealed unexpected features of the roles platelets play in enhancing metastasis.
The metastasis-enhancing effects of platelets have most often been attributed either to their ability to promote cell adhesion or to their capacity to surround and protect cancer cells as they migrate through the bloodstream and stick to a secondary site. But platelets are also loaded with growth factors that could affect the behavior of cancer cells, “and that hadn’t really been explored,” says Hynes.
“The first thing I tried was to see whether pretreating tumor cells with platelets would promote metastasis,” Labelle says. The answer was a resounding yes: mice injected with colon and breast cancer cells that had been incubated along with platelets—and then rinsed, to rule out platelets’ known adhesion properties—showed a marked increase in metastasis to the lungs.
In this image, metastatic colon cancer (green) interact with platelets (red) in sections from mouse lungs. Platelets provide pro-metastatic signals to cancer cells via direct contact. These signals induce a change in shape consistent with a process known as epithelial-mesenchymal transition.
Image: Myriam Labelle
At the same time, Labelle noticed that cancer cells that had been directly exposed to platelets grew longer and thinner. That change in shape is consistent with a process known as epithelial-mesenchymal transition (EMT), which increases the capacity of cells to migrate and invade. EMT is involved in metastasis, and it is known to be enhanced by TGF-beta, one of the growth factors present in platelets. Gene expression array analysis of the platelet-treated cancer cells showed increased activation of EMT-related genes and of genes responding to TGF-beta.
Illustration: VSA Partners