For the first time ever, Stanford University researchers have successfully transformed normal human tissue into three-dimensional cancers in a tissue culture dish.
Watching how the cells behave as they divide and invade surrounding tissue will help physicians better understand how human cancers act in the body. The new technique also provides a way to quickly and cheaply test anti-cancer drugs without requiring laboratory animals.
"Studies of this type, which used to take months in animal models, can now occur on a time scale of days," Nature quoted Paul Khavari of the Stanford, as saying.
The researchers focused on epithelial cells, which line the surfaces and cavities of the body. Cancers of epithelial cells make up approximately 90 percent of all human cancers.
The researchers worked with normal human epithelial cells gathered from surgical samples from skin, cervix, esophagus and throat. Unlike cancer cell lines, some of which have been grown in laboratories around the world for years, these primary cells were minimally cultured.
To make these normal cells cancerous, the researchers used viruses to tweak just two genetic pathways known to be involved in uncontrolled growth. One drives cells forward in the cell cycle while the other disables an internal checkpoint that normally blocks abnormal proliferation.
Many naturally occurring human cancers display identical genetic changes, and the researchers found that simultaneously altering the two pathways is highly effective at transforming normal cells.
Khavari and Ridky then added the altered, pre-cancerous epithelial cells to a tissue culture dish containing other components of human skin.
They found that at first the cells nestled down on the basement membrane and formed what looked like a normal, three-dimensional cross-section of skin. But within about six days, the cells started to behave more ominously - punching through the membrane and invading the stromal tissue below.
"Cells go from a pre-malignant state to invasive cancers, often over the course of years. Only in this intact, human-tissue model it occurs much more quickly," said Khavari.hen the researchers examined the patterns of gene expression in the newly cancerous cells, they found that the patterns closely matched the genetic profiles of spontaneously occurring human cancers.
But when the cells were grown in a single layer, without the basement membrane, stroma and normal three-dimensional tissue structure, their gene expression profiles were markedly different.