Glioblastoma multiforme (GBM) is the most aggressive tumour of the central nervous system. Its infiltrative nature prevents complete surgical removal, and growth and recurrence depend on the conditions prevailing in the microenvironment in which the tumour develops, in the early stages of tumorigenesis. An international team of scientists analysed how these conditions affect the progression of GBM.

'We have developed a mathematical model that takes into account the ploidy of tumour cells and the brain microenvironment, allowing to simulate the growth and spread of the tumour', Zuzanna Nowicka from the Department of Biostatistics and Translational Medicine of the Medical University of Lodz, the first author of the publication in „Cancer Research”. 

Ploidy describes the amount of genetic material in a cell. For example, in reproductive cells, humans have 23 chromosomes. In a fertilised cell (and in the offspring that is created from it), the amount of genetic material doubles. Therefore, healthy body cells (somatic cells) are equipped with 23 chromosomes from the mother and 23 from the father, i.e. there are 46 of them in the cell nucleus (the so-called diploid genome, ‘2n’). Sometimes, during fertilisation, an aberration occurs, and as a result, the offspring's body cells have 47 chromosomes. This happens in so-called trisomies - Down syndrome and Klinefelter syndrome.

However, it turns out that ploidy - or the number of chromosomes - changes in some cells during the life of the organism. This is usually related to the formation of dangerous mutations that contribute to the development of cancer. There are cancer cells with 48, 60 or even 92 chromosomes (this is called whole genome doubling – WGD, which results in a tetraploid 4n genome).

The scientists took the ploidy of cancer cells into account in their research. They decided to investigate how it affects the development of GBM. Because the more genes in a cell, the more energy is needed for them to function. 'Our research indicates that high ploidy cells can switch to anaerobic metabolism more quickly because they are more sensitive to hypoxia', comments Zuzanna Nowicka.

In addition, the rate of cancer recurrence depended on the brain's microenvironment. 'Analysis of historical data showed that the level of oxygen in a given organ correlated with the typical ploidy of tumours that developed there', Nowicka comments. If a part of the brain or an organ was more oxygenated (as in lung tissue), cancer cells with a larger number of chromosomes could survive there. In turn, where the environment was poor in oxygen and nutrients, cancer cells only achieved a lower ploidy. 'The results of the study indicate that the availability of nutrients in the brain affects the condition of cancer cells, and thus the development and recurrence of GBM. This is an important step towards a better understanding of this deadly cancer and the development of more effective treatment strategies', Nowicka says.

The papers in Cancer Research is the result of collaboration with an international group of scientists, including researchers from Moffitt Cancer Center (Florida), Icahn School of Medicine at Mount Sinai (New York) and San Diego State University (California).

Ludwika Tomala (PAP)

PAP - Science in Poland

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