Mitochondrial Respiration in Human Colorectal and Breast Cancer Clinical Material Is Regulated Differently.

Andre Koit,Natalja Timohhina,Lyudmila Ounpuu,Marju Puurand,Vahur Valvere,Igor Shevchuk,Rita Guzun,Vladimir Chekulayev,Tuuli Kaambre,Aleksandr Klepinin,Laura Truu,Karoliina Heck,Kersti Tepp

doi:10.1155/2017/1372640

Abstract

We conducted quantitative cellular respiration analysis on samples taken from human breast cancer (HBC) and human colorectal cancer (HCC) patients. Respiratory capacity is not lost as a result of tumor formation and even though, functionally, complex I in HCC was found to be suppressed, it was not evident on the protein level. Additionally, metabolic control analysis was used to quantify the role of components of mitochondrial interactosome. The main rate-controlling steps in HBC are complex IV and adenine nucleotide transporter, but in HCC, complexes I and III. Our kinetic measurements confirmed previous studies that respiratory chain complexes I and III in HBC and HCC can be assembled into supercomplexes with a possible partial addition from the complex IV pool. Therefore, the kinetic method can be a useful addition in studying supercomplexes in cell lines or human samples. In addition, when results from culture cells were compared to those from clinical samples, clear differences were present, but we also detected two different types of mitochondria within clinical HBC samples, possibly linked to two-compartment metabolism. Taken together, our data show that mitochondrial respiration and regulation of mitochondrial membrane permeability have substantial differences between these two cancer types when compared to each other to their adjacent healthy tissue or to respective cell cultures.

Highlights

The field of cellular bioenergetics is gaining increased attention and studies performed during the last years have shown that targeting cancer cell energy metabolism may be a new and promising area for selective tumor treatment [1]
Our results confirmed that respiratory capacity is preserved in both human breast cancer (HBC) and human colorectal cancer (HCC) as these both demonstrated substantial rates of oxidative phosphorylation, which contradicts with earlier widespread understanding that the metabolism of human breast and colorectal carcinomas is prevalently glycolytic
Our results indicated that apparent glycolytic nature of some breast cancer types could be expected based on cell cultures, but this presumption was in sharp conflict when culture cell results were compared with these from respective clinical samples

Summary

Introduction

The field of cellular bioenergetics is gaining increased attention and studies performed during the last years have shown that targeting cancer cell energy metabolism may be a new and promising area for selective tumor treatment [1]. Majority of previous studies about the bioenergetics of malignant tumors were performed in vitro on different cell models with the conclusion that cancer cells have increased glucose uptake and, due to mitochondrial damage, it is not metabolized via oxidative phosphorylation (OXPHOS) [2,3,4]. A new concept for tumor metabolism was proposed—metabolic coupling between mitochondria in cancer cells and catabolism in stromal cells—which promotes tumor growth and development of metastases. The cancer cells will metabolize these fuels via their tricarboxylic acid cycle and OXPHOS [8,9,10]. Complex interplay between developing cancer cells and host physiology, possibly mediated by “waves” of gene expression

Methods

Results

Conclusion