Selective changes in cholesterol metabolite levels in plasma of breast cancer patients after tumor removal
Abstract
Oxygenated metabolites of cholesterol belong to a large group called oxysterols [1]. Oxysterols are formed in the human body or ingested in the diet.
Despite their low tissue levels, oxysterols play important roles in the organism and, e.g. through interaction with liver X receptors, oxysterol-binding proteins, or drug transporters, can influence both carcinogenesis and cancer progression [2]. The role of cholesterol and oxysterols in breast cancer currently receives increasing attention due to the fact that patients have higher cholesterol levels than healthy controls [3], and enzymes of biosynthesis of cholesterol, 25-hydroxycholesterol, and 7-hydroxycholesterol contribute to endocrine therapy (e.g. tamoxifen or aromatase inhibitors) resistance in breast cancer models in vitro [4].
Additionally, B-ring oxysterols (e.g. 7-ketocholesterol) are suspected to influence hormonal treatment efficacy via interaction with the antiestrogen binding site and estrogen receptors in tumor cells [5]. The present study explored the question of feasibility of detection of selected oxysterols (7α-hydroxycholesterol, 7-ketocholesterol, 25-hydroxycholesterol, and 27-hydroxycholesterol) in plasma of breast cancer patients.
This approach provides basic information about the method suitability, individual variability, and detection limits of oxysterols in circulation of patients before a larger detailed study can be performed. We also asked whether tumor removal causes detectable perturbations in levels of oxysterols that could then be used, e.g. for estimation of the disease risk or monitoring of its recurrence.