Glycerophosphoglycerol, Beta-alanine, and pantothenic Acid as metabolic companions of glycolytic activity and cell migration in breast cancer cell lines.

Antje Hutschenreuther,Gerd Birkenmeier,Knut Krohn,Claudia Birkemeyer,Marina Bigl

doi:10.3390/metabo3041084

Antje Hutschenreuther, Gerd Birkenmeier + Show 3 more

Open Access

https://doi.org/10.3390/metabo3041084

Copy DOI

Journal: Metabolites	Publication Date: Nov 27, 2013
Citations: 22	License type: CC BY 4.0

Affiliation: Leipzig University

Abstract

In cancer research, cell lines are used to explore the molecular basis of the disease as a substitute to tissue biopsies. Breast cancer in particular is a very heterogeneous type of cancer, and different subgroups of cell lines have been established according to their genomic profiles and tumor characteristics. We applied GCMS metabolite profiling to five selected breast cancer cell lines and found this heterogeneity reflected on the metabolite level as well. Metabolite profiles of MCF-7 cells belonging to the luminal gene cluster proved to be more different from those of the basal A cell line JIMT-1 and the basal B cell lines MDA-MB-231, MDA-MB-435, and MDA-MB-436 with only slight differences in the intracellular metabolite pattern. Lactate release into the cultivation medium as an indicator of glycolytic activity was correlated to the metabolite profiles and physiological characteristics of each cell line. In conclusion, pantothenic acid, beta-alanine and glycerophosphoglycerol appeared to be related to the glycolytic activity designated through high lactate release. Other physiological parameters coinciding with glycolytic activity were high glyoxalase 1 (Glo1) and lactate dehydrogenase (LDH) enzyme activity as well as cell migration as an additional important characteristic contributing to the aggressiveness of tumor cells. Metabolite profiles of the cell lines are comparatively discussed with respect to known biomarkers of cancer progression.

Highlights

Breast cancer, the most common cancer among women worldwide, is known to be a highly heterogeneous disease
Since breast cancer cells were shown to comply with the Warburg hypothesis [13], we examined metabolites belonging to glycolysis and the tricarboxylic acid (TCA) cycle in more detail
Our results emphasize the potential of metabolite profiling as a non-targeted approach for classification of known cancer subtypes

Summary

Introduction

The most common cancer among women worldwide, is known to be a highly heterogeneous disease. It was shown to be distinguishable, for example, according to cell differentiation grade, histological origin, or gene expression profile [1,2,3]. Recent genomic studies classified different subtypes of breast cancer with different prognosis for the clinical outcome [2,4]. Only few studies about comparative metabolite profiling of breast cancer cell lines are available. Metabolite profiling has been used in the past as a sensitive screening method to identify various tumor-associated biomarkers in tumor biopsies such as sarcosine, glycine, alanine, myo-inositol, lactate and phospholipids [8,9]. Metabolite profiling has been applied in distinguishing cancer types and in cancer diagnostics [10]

Objectives

Results

Conclusion