Interplay of choline metabolites and genes in patient-derived breast cancer xenografts.

Introduction: Dysregulated choline metabolism is a well-known feature of breast cancer, but the underlying mechanisms are not fully understood. In this study, the metabolomic and transcriptomic characteristics of a large panel of human breast cancer xenograft models were mapped, with focus on choline metabolism.

Methods: Tumor specimens from 34 patient-derived xenograft models were collected and divided in two.

Subtype-specific response to bevacizumab is reflected in the metabolome and transcriptome of breast cancer xenografts.

Antiangiogenic therapy with bevacizumab has shown varying results in breast cancer clinical trials. Identifying robust biomarkers for selecting patients who may benefit from such treatment and for monitoring response is important for the future use of bevacizumab. Two established xenograft models representing basal-like and luminal-like breast cancer were used to study bevacizumab treatment response on the metabolic and gene expression levels.

Ischemia caused by time to freezing induces systematic microRNA and mRNA responses in cancer tissue.

Time to freezing tumor tissue for RNA expression analysis will always vary to some extent. To evaluate the effect of ischemia time, tumor tissue from ten breast cancer patients was collected and aliquots of tissue were snap frozen at different time points after surgery (0, 0.5, 1, 3 and 6 h).

13C high-resolution-magic angle spinning MRS reveals differences in glucose metabolism between two breast cancer xenograft models with different gene expression patterns.

Tumor cells have increased glycolytic activity, and glucose is mainly used to form lactate and alanine, even when high concentrations of oxygen are present (Warburg effect). The purpose of the present study was to investigate glucose metabolism in two xenograft models representing basal-like and luminal-like breast cancer using (13) C high-resolution-magic angle spinning (HR-MAS) MRS and gene expression analysis. Tumor tissue was collected from two groups for each model: untreated mice (n=19) and a group of mice (n=16) that received an injection of [1-(13) C]-glucose 10 or 15 min before harvesting the tissue.

Merging transcriptomics and metabolomics--advances in breast cancer profiling.

Background: Combining gene expression microarrays and high resolution magic angle spinning magnetic resonance spectroscopy (HR MAS MRS) of the same tissue samples enables comparison of the transcriptional and metabolic profiles of breast cancer. The aim of this study was to explore the potential of combining these two different types of information.

Methods: Breast cancer tissue from 46 patients was analyzed by HR MAS MRS followed by gene expression microarrays.

Distinct choline metabolic profiles are associated with differences in gene expression for basal-like and luminal-like breast cancer xenograft models.

Background: Increased concentrations of choline-containing compounds are frequently observed in breast carcinomas, and may serve as biomarkers for both diagnostic and treatment monitoring purposes. However, underlying mechanisms for the abnormal choline metabolism are poorly understood.

Methods: The concentrations of choline-derived metabolites were determined in xenografted primary human breast carcinomas, representing basal-like and luminal-like subtypes.