New research demonstrates that previous models used to
examine cancer may not be complex enough to accurately
mimic the true cancer environment. Using oral cancer cells in a 3D model of laboratory-made
tissue that mimics the lining of the oral cavity, the researchers found that
the tissue surrounding cancer cells can epigenetically mediate, or temporarily
trigger, the expression or suppression of a cell adhesion protein associated
with the progression of cancer. These new findings support the notion that
drugs that are currently being tested to treat many cancers need to be screened
using more complex tissue-like systems, rather than by using conventional Petri
dish cultures that do not fully manifest features of many cancers.
“Research on cancer progression has been drawn largely using
models that grow cancer cells in plastic dishes. Our research reveals a major
shortcoming in the experimental systems used to study cancer development. When
using simplified culture systems in which cells are grown on plastic, cancer
cells grow as a 2D monolayer and lack the 3D tissue structure seen in human
cancer. As a result, complex interactions that occur between the cancer cells
and the surrounding tissue layers are not accounted for,” said first author
Teresa DesRochers, PhD, a graduate of the Sackler School of Graduate Biomedical
Sciences at Tufts, currently in the Department of Biomedical Engineering at
Tufts University School of Engineering.
The researchers report that the 3D network of cell
interactions activates epigenetic mechanisms that control whether genes
critical for cancer development will be turned on or off. By imitating the
structure of the tumor microenvironment seen in different stages of cancer, the
research team was able to observe that cell-to-cell interactions that are
inherent in tissue structure are sufficient to turn on the cell adhesion
protein, E-cadherin, which can delay cancer development.
Since both invasion and metastasis occur when cells break
away from the primary cancer site, an event correlated with loss of E-cadherin,
treating cancers to induce re-expression of this protein through epigenetic
control may be an important way to control cancer progression.
“Our findings show the reversible nature of E-cadherin when
cancer cells are placed in a 3D network of cells that mimics the way cancer
develops in our tissues. This confirms that cancer biology needs to move into
the ‘third dimension’ where cancer cells can be studied in a network of other
cells that can control their behavior. We know now that the plastic dish alone
is not good enough,” said senior author Jonathan Garlick, DDS, PhD, a professor
in the Oral and Maxillofacial Pathology Department at Tufts University School
of Dental Medicine.
This study is published in Epigenetics.
