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Recently a PhD student of the TTÜ Chemistry and Gene Technology study programme Andre Koit defended his doctoral thesis “Malignant Transformation Causes Rearrangement of Energy Metabolism in Colorectal and Breast Cancers”.
Cancer poses an increasing burden for the Western world healthcare systems in particular due to ageing society, lifestyle choices and environmental problems. A similar situation is also true for Estonia where deaths due to malignancies are on the second place after deaths caused by cardiovascular diseases.
The supervisor of the doctoral thesis, Research Professor at National Institute of Chemical Physics and Biophysics Tuuli Käämbre says, “Malignant tumours can be curable if diagnosed in early stages and for that reason many screening programs have been initiated also in Estonia for early detection of breast, colorectal and cervical cancers. Screening programs are sometimes associated with certain problems (such as overdiagnosis), however, in Estonia an even greater problem is caused by people who decide not to participate in the screening programs.“
So far cancer has been considered to be in particular a genetic disease, but it has become increasingly evident that there are numerous changes to metabolism that cannot be usually attributed to genetic causes. Even though changes in glucose metabolism were first described more than a century ago, still many controversies exist, which in turn indicates the need for further research.
“In this doctoral thesis we used both human clinical material and cell cultures to describe and compare functional changes in oxidative phosphorylation in breast and colorectal cancers,” Tuuli Käämbre explains.
Relations between respiratory properties of breast cancer and the expected disease aggressiveness were examined by using human samples and relevant cell lines. Striking difference emerged as opposing relation between respiratory capacity and tumor agressivness in human breast cancer samples and in vitro cell lines indicating severe biological differences between these two sample types. This may imply the reasons why the underlying biology of cell cultures and human samples might often come to conflicting results and hinder translational research. Further analysis suggested presence of two populations of differently regulated mitochondria in human breast cancer samples – a result which was not found in colorectal cancer samples. In case of colorectal cancer it appeared, however, that the patients with rapid ATP (substance that supplies cells with energy) production had worse prognosis than the ones with low mitochondrial respiration rate. This illustrates that there can be different causes that lead to formation of cancer cells, which can ensure their homeostasis, i.e. the property to maintain a favourable environment for development.
Research Professor Tuuli Käämbre says, “The results of the thesis highlight the elevated need to run functional studies on biological samples as static methods widely used today might not be sufficient to describe the underlying biological processes, their activity and extent.”
Supervisors: Research Professor Tuuli Käämbre (National Institute of Chemical Physics and Biophysics) and Dr. Vahur Valvere (North Estonia Medical Centre).
Opponents: Dr. Eric Dufour (University of Tampere) and Researcher Maili Jakobson (University of Tartu).
The doctoral thesis has been published in the digital collection of TTÜ library: https://digi.lib.ttu.ee/i/?9349
Additional information: Research Professor at National Institute of Chemical Physics and Biophysics Tuuli Käämbre, tuuli.kaambre@kbfi.ee
Original post by Tallinn University of Technology
