13. 12. 2018

Cancer cells with damaged mitochondrial DNA (mtDNA), which is necessary for mitochondrial respiration, are unable to form tumors. Researchers from the Institute of Biotechnology of the CAS in the BIOCEV centre have already proven that in order to be able to do so, cancer cells need to restore respiration through “stealing” of mitochondria with undamaged mtDNA from surrounding non-cancer cells. Now a subsequent research has managed to explain why respiration is so important for the creation of tumors.

“Mitochondria are small intercellular formations which produce energy necessary for a number of processes including cell growth which is an elementary prerequisite for tumor tissue,” states Professor Jiří Neužil, head of the Laboratory of Molecular Terapy in the Institute of Biotechnology. “Production of energy in mitochondria is dependent on mitochondrial ‘breathing’ (respiration), i.e. consumption of oxygen. An important property of mitochondria is presence of genetic information – mtDNA, which is essential for the process of respiration,” explains Neužil.

Connection between the disability to form tumors and insufficient energy has not been verified, however, and scientists had to look for a new way. They found out that the reason for the disability was the fact that mitochondrial respiration takes part in the creation of pyrimidines – building blocks of DNA whose creation is necessary for cell growth.

Cancer cells with mtDNA defects do not respire and therefore cannot form pyrimidines. This blocks their growth as well as growth of the whole tumor. Research conducted on laboratory mice has shown that after gaining mitochondria from surrounding cells and restoring respiration, cancer cells are once again able to produce pyrimidines and grow. The tumor starts to re-emerge.

A hope for new medicaments

“Our findings, published in the prestigious journal Cell Metabolism, are of great interest both in terms of basic research and terms of its possible transfer into medicinal practice,” says Neužil in regard of possible medicinal applications of the new knowledge. “The abovementioned mechanism could be shared among many tumor types because rapid growth – which requires intensive creation of pyrimidines – is one of universal properties of cancer cells. We anticipate that these findings will facilitate development of new, wide-spectrum anti-cancer agents.”

Abstract and other information on the article published in Cell Metabolism can be found here.

The image shows cancer cells 0, 10, 20 and 60 days after insertion into the host (mouse) and shows how the cells gradually renew their mtDNA. Cell nuclei are highlighted in blue, mitochondria in red, and mtDNA in green

Prepared by: Milan Pohl, Department of Media Communication of the Head Office of the CAS, based on a press release by the Institute of Biotechnology of the CAS
Photo: Institute of Biotechnology of the CAS