Stromal-epithelial Cell Interactions In Mammary Cancer: A Role For Fatty Acids

De novo fatty acid (FA) synthesis is an important part of cancer progression as proliferating cancer cells need a continuous supply of lipids for membrane production.  Synthesized FA are used for energy production through β-oxidation and lipid modification of proteins.  Potentially, the de novo FA synthesis pathway represents an excellent target for cancer therapeutics.  Our lab developed an ex vivo co-culture system for studying breast cancer, which was verified by CARS microscopy to be a mimic of the tumor microenvironment.  This system has allowed us to investigate various aspects of tumor progression including growth and migration.  We demonstrated that adipose tissue alone is capable of stimulating growth and migration of the rat mammary epithelial tumor cell line CRL1743. Conditioned media (CM) from co-culture experiments induced CRL1743 cell proliferation, while removal of FA from CM demonstrated an inhibition.  Gas chromatography analysis of the co-culture experiments demonstrated that, when tumor cells are present, there is an increase in FA of the de novo synthesis pathway in the tumor cells, CM, and tissue samples collected. Further investigation needs to be done to define the role of palmitoleic acid, linoleic acid, and oleic acid on tumor cell proliferation as these FA were identified as having the most significant change.  This co-culture model is an excellent intermediate between 2D in vitro cell culture studies and costly in vivo studies.  Use of this co-culture system will provide a means by which we can study the effect of cancer therapeutics targeting the de novo FA synthesis pathway.