## Properties of tumour cells

Although different types of tumours may behave very differently in the same patient, certain features are typical for tumour cells in general (Figure 9.6). There are 10 typical characteristics of tumour cells, of which the first 6 features are critical for human cells to undergo a cancerous transformation and form a malignant tumour:

1. Signalling for non-permanent division - In healthy cells, cell division is activated by the binding of a growth factor to a receptor on the cell surface, which triggers a whole cascade of events. Tumour cells have mechanisms capable of constant signalling that drive the cell to divide more and more, either by activating division independently of growth factors (a mutation in the receptor that causes it to always be activated), or the tumour cell can produce many of its own growth factors which it can respond to itself.

2. Resistance to division suppressors - Neighbouring cells normally produce molecules that signal tumour cells to stop dividing. However, the tumour cells ignore these signals, often due to decreased production of receptors that should catch them. The signal to stop dividing should also be contact inhibition, where the cell bumps into other surrounding cells while dividing, so it decides to stop dividing (so they all fit into place). Tumour cells, however, bypass this control mechanism and continue to divide.

3. Resistance to cell death - The surrounding healthy cells notice that uncontrolled division of some cells is taking place, which negatively affects them by depriving them of nutrients and physically limiting them. Therefore, the healthy cells send signals to the tumour cells, prompting them to undergo programmed cell death. However, the tumour cells fight back by activating factors that prevent death or inactivating factors that lead to death.

4. Replicative immortality – With some exceptions, all healthy cells can undergo only a limited number of divisions before they become old. Linear chromosomes loose DNA at their ends (telomeres) and after reaching a certain number of copies DNA is no longer copied. Tumour cells often circumvent this problem by possessing a functional telomerase enzyme (more on this in Chapter 3 - DNA as the bearer of genetic information) that enables them to replace these lost DNA. Apart from tumour cells, only embryonic cells, germ cells, and stem cells have this ability. Thanks to the ability to maintain the telomeres, tumour cells practically do not age and can divide relatively indefinitely. The disruption of the function of proteins involved in the interruption of division also contributes to this.

5. Invasive growth and metastasis – Tissue-forming cells are not free but bound to each other through the extracellular matrix. Tumour cells can break bonds in their environment, break free from the tissue, and migrate through the blood system to the rest of the body where they can metastasize.

6. Induction of angiogenesis - Rapidly dividing tumour cells have a high demand for the supply of nutrients and oxygen. To achieve a more efficient supply, they create their own blood vessels that direct blood into circulation. The newly formed vascular network is functionally and structurally imperfect, which poses risks to the supply of the tumour.

7. Deregulation of cellular energetics - Despite the formation of blood vessels during rapid tumour growth, there is a lack of oxygen for the cells located in the tumour. The cells solve this deficiency by switching their metabolism to another metabolic pathway that is independent of oxygen. This leads to a change in the characteristics of the tumour cells and their environment.

8. Tumour-induced inflammation - It is known that immune cells are also part of the tumour mass, often invading and causing inflammation to destroy the tumour. These include, for example, CD8+ cytotoxic T-lymphocytes or natural killer cells. Other immune cells also arrive at the site of inflammation to produce growth factors and promote the formation of new blood vessels to heal the inflammation or injury. However, growth factors can also trigger excessive division of tumour cells. As a result, up to 20% of tumours develop at the site of chronic infection, for example, in a stomach colonized by the bacterium Helicobacter pylori, resulting in long-term inflammation. Another example is the autoimmune disease Crohn's disease, which can lead to colorectal cancer, or a liver infection with the hepatitis B or C virus, which promotes the formation of hepatocellular carcinoma under certain circumstances.

9. Escape from the immune system - The human body can recognize foreign particles such as viruses, bacteria, or even its own cells when they get sick. When the body recognizes them, the target is marked which triggers an immune response that eventually eliminates it. In the case of tumour cells, the tumour controls a mechanism that allows it to evade the immune system's efforts to destroy it. It does this, for example, by trying to hide from the immune system by altering the proteins on the surface of the cell that might cause the immune system to recognize it.

10. Instability of the genome - Point mutations, small or large duplications, deletions, translocations, or chromosomal aneuploidies are very common in tumours, as discussed in Chapter 5 - Mutations: How they arise and what to do with them. Interestingly, DNA mutations in tumour cells are rare in paediatric cases (only about 0.1 bases per million bases), but in tumours such as lung cancer or skin melanomas that are caused by mutagens, the frequency of DNA mutations is 1000 times greater, up to 100 mutations per million bases.