Three-Dimensional Growth Encourages Expression of Epigenetic Changes in Tumors

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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