Three-Dimensional Growth Encourages Expression of Epigenetic Changes in Tumors

A team of biomedical engineers has found that growing cultures of cancer cells in two-dimensional Petri dishes fails to elicit epigenetic changes in the cells that occur when three-dimensional growth chambers are used.

In order to examine better the microenvironment surrounding a tumor, investigators at Tufts University (Boston, MA, USA) grew oral cancer cells in a three-dimensional model of lab-made tissue that mimicked the lining of the oral cavity.

They reported in the January 2012 issue of the journal Epigenetics that use of bioengineered human tissue constructs that mimic the complexity of their in vivo counterparts revealed that the tumor microenvironment could direct the reexpression of E-cadherin through the reversal of methylation-mediated silencing of its promoter.

Cadherins (named for “calcium-dependent adhesion”) are a class of type-1 transmembrane proteins. They play important roles in cell adhesion, ensuring that cells within tissues are bound together. They are dependent on calcium (Ca2+) ions to function, hence their name. It has been observed that cells containing a specific cadherin subtype tend to cluster together to the exclusion of other types, both in cell culture and during development.

Loss of E-cadherin function or expression has been implicated in cancer progression and metastasis. E-cadherin downregulation decreases the strength of cellular adhesion within a tissue, resulting in an increase in cellular motility. This in turn may allow cancer cells to cross the basement membrane and invade surrounding tissues.

Treating cancers to induce reexpression of E-cadherin 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 three-dimensional 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 Dr. Jonathan Garlick, professor of oral and maxillofacial pathology at Tufts University.

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