Tiny windows in mice show cancer spread in real-time
Researchers injected mice with cancer cells designed to glow and examined mice's abdomens through windows to determine cancer cells' growth.
Thu, Nov 01 2012 at 2:11 PM
To literally watch cancer spread, researchers have surgically implanted small glass windows into the bellies of living mice.
The insights such windows could yield on cancer might help better battle it, scientists added.
In the last decade, researchers have developed tiny glass windows they could implant on the skin and mammary glands of living mice. These have enabled scientists to use microscopes to watch how breast cancer and tumors under the skin develop in real-time.
However, until now, investigators lacked windows that could help them peer at the liver, spleen, lungs, bone marrow and lymph nodes, the internal organs and tissues most prone to metastasis, the process by which cancers spread from one area to distant sites elsewhere in the body. Most cancer-related deaths are caused by metastasis, and the long-term aspects of this lethal dispersal remain largely unknown.
Now scientists have developed windows they can implant into the abdominal walls of mice, giving them a direct view of the rodents' spleen, kidney, small intestine, pancreas and liver.
"Our abdominal window works exactly the same as the small windows of an airplane," researcher Jacco van Rheenen, a medical physicist at the Hubrecht Institute in the Netherlands, told LiveScience.
The windows, which consist of reusable titanium rings with tiny glass panes about a half-inch (1.2 centimeters) wide on top, are tightly secured in the skin and abdominal wall with stitches. The windows did not impair the rodents' movements, and they caused no signs of inflammation or infection, although the glass panes did break in about 3 percent of all cases. [See Video of Cancer Spread in Real-Time]
The window helped to visualize abdominal organs for five weeks on average before the stitches loosened. "We can potentially stretch the time the window remains in the animal by, for example, using metal sutures — however, there was no need for this in our experiments," van Rheenen said.
The researchers injected the mice with cancer cells genetically engineered to give off a glow, allowing the scientists to microscopically monitor these cells in the liver over the course of 14 days. Surprisingly, they saw that some cells within a metastatic cancer were very mobile in its early stages of formation, even before the cancer had spread. During this early stage, cell mobility was apparently needed before the number of cells increased.
"This was not found before, becauseprior studies used techniques that study fixed and dead tissues, which provide only a snapshot of one moment in time and lack the crucial information on the behavior of the cell before and after this snapshot," van Rheenen said. "This makes it difficult to study growth and spread."
"The real-time visualization of tumor growth shows that tumor cells are much more dynamic than we anticipated based on the snapshot images," van Rheenen said. "For example, it has been assumed that cell movement is not required once cells have established a new, distant tumor site. In our paper, we spy on colorectal cancer cells that colonize the liver in real-time and showed that tumor cell movement can still be important even during the formation of metastases."
The investigators suggest that cell movement might first help spread cancer cells from a tumor to other parts of the body and later supports the growth of these cells into new tumors. They found that a drug that suppressed cell movement during the early phases of metastasis formation could help fight metastasis in mice, hinting at a new strategy for fighting cancer.
"However, further research is required to determine whether and to what extent this data can be translated to humans," van Rheenen said.
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