“During work with non-neoplastic cells, one needs to provide what is necessary for them to form structures that will look and behave like a normal structure,” explained Sophie A. Lelièvre, Ph.D., associate professor at Purdue University.
The majority of cancers have epithelial origins, and to experimentally reproduce the phenotype of non-neoplastic epithelial cells, it is imperative to check for several things.
“One of them is polarity,” noted Dr. Lelièvre. All epithelial cells are polarized, with a basal side facing the ECM and an apical side facing the outside, which can be the blood vessel lumen, the lung alveoli, or the breast ductal system.
Dr. Lelièvre and collaborators have shown that maintaining apical polarity in epithelial cells is more sensitive to culture conditions than maintaining basal polarity. The full polarity of non-neoplastic cells is one of the most difficult aspects to preserve in vitro but represents one of the most important requirements to faithfully reproduce tissues phenotypically in vitro.
If cultures are grown with cells that are only partially differentiated, which means that they have basal but not apical polarity, those cells are already in a different state, they are already primed into the cell cycle, and the experimental conditions are not exploring a fully differentiated system.
“That is an important concept when studying cancer, because non-neoplastic tissue is fully polarized,” said Dr. Lelièvre. “In order to understand cancer, it is essential to first understand how a fully polarized cell becomes partially polarized. Otherwise, by starting with cells that are not fully polarized, one could miss an important step,” she added.
Dr. Lelièvre and collaborators have developed what they say is the first high-throughput culture system for non-neoplastic cells. This valuable tool will make it possible to study that impact of carcinogenic factors, such as environmental exposures, an important facet of preventive research.