The Chemical Potential of Cholesterol Regulates the Pro-Metastatic Phenotype in a Cell Culture Model of Breast Cancer

Abstract

We have developed a simple and reliable method to determine the chemical potential of cholesterol in plasma membranes of living cells in vitro. For a variety of cultured cells, including non-metastatic breast cancer cells, the chemical potential of cholesterol is maintained at a level of about −1.9 kBT per moleculerelative to crystalline cholesterol. But for a metastatic breast cancer cell line, this chemical potential is appreciably greater, at about −0.7 kBT per molecule. In light of these observations and recent reports of cholesterol's role in breast cancer progression we have developed a method to alter and maintain the chemical potential of cholesterol in plasma membranes of cultured cells at any desired level. Through this technique, we lowered the chemical potential of cholesterol in the metastatic cell line to that of the non-metastatic line and found that this significantly reduced the expression levels of several key proteins implicated in breast cancer progression and metastatic spread.