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Studying Cells in 3-D
A reflection confocal micrograph
of collagen fibers of a 3-D matrix
with cancer cells embedded;
A new study led by Johns Hopkins University engineers indicates it may happen. Looking at cells in 3-D, the team members concluded, yields more accurate information that could help develop drugs to prevent cancer's spread.
"Finding out how cells move and stick to surfaces is critical to our understanding of cancer and other diseases. But most of what we know about these behaviours has been learned in the 2-D environment of Petri dishes," said Denis Wirtz, principal investigator of the study. "Our study demonstrates for the first time that the way cells move inside a three-dimensional environment, such as the human body, is fundamentally different from the behaviour we've seen in conventional flat lab dishes. It's both qualitatively and quantitatively different."
One implication of this discovery is that the results produced by a common high-speed method of screening drugs to prevent cell migration on flat substrates are, at best, misleading, said Wirtz. This is important because cell movement is related to the spread of cancer. "Our study identified possible targets to dramatically slow down cell invasion in a three-dimensional matrix."
When cells are grown in two dimensions, certain proteins help to form long-lived attachments called focal adhesions on surfaces. Under these 2-D conditions, these adhesions can last several seconds to several minutes. The cell also develops a broad, fan-shaped protrusion called a lamella along its leading edges, which helps move it forward. "In 3-D, the shape is completely different," Wirtz said. "It is more spindlelike with two pointed protrusions at opposite ends. Focal adhesions, if they exist at all, are so tiny and so short-lived they cannot be resolved with microscopy."
The study's lead author, Stephanie Fraley, said that the shape and mode of movement for cells in 2-D could produce misleading results when testing the effect of different drugs.
"It is much more difficult to do 3-D cell culture than it is to do 2-D cell culture," Fraley said. "Typically, any kind of drug study that you do is conducted in 2-D cell cultures before it is carried over into animal models. Sometimes, drug study results don't resemble the outcomes of clinical studies. This may be one of the keys to understanding why things don't always match up."
Wirtz added that "because loss of adhesion and enhanced cell movement are hallmarks of cancer," his team's findings should radically alter the way cells are cultured for drug studies.
MEDICA.de; Source: Johns Hopkins University