discovery
Cancer cells have altered DNA

Cancer Cells

More than one in three adults in the industrialized world will be affected by a cancer diagnosis, and there are many factors that contribute to this1. If you are interested to read more about some of the topics in this article, see our articles on Carcinogens and What Causes Cancer. There are also a number of other Video Resources, on how people at risk of cancer, or affected by a cancer diagnosis, can make healthful choices about nutrition and lifestyle.

Key points:

  • All living organisms are composed of cells, these cells reproduce themselves by dividing
  • Our body tissues are composed of many different types of cells that have different functions
  • Stem cells are parent cells in body tissues that can produce different types of cells by cell division, and by switching on appropriate genes for that cell type
  • Cell division or replication is a complex process involving copying the DNA and separating out the two sets of copies, and placing one set in each half of the cell as it splits to form two daughter cells
  • Mistakes in the DNA replication process can cause mutations, and other factors can damage the DNA during the life of the cell
  • Mutations in the DNA can cause healthy cells to become cancer cells
  • If these mutations persist, the cell adopts different behavior, ignoring the normal controls on cell division, and keeps dividing
  • Cancer cells survive because they ignore the ‘self-destruct’ process that should remove cells with abnormalities
  • Cancer stem cells are stem cells that can continue to produce more cancer cells, and even when a cancer has been removed, the cancer stem cells may persist and be a source of cancer recurrence
  • More advanced cancers have acquired more DNA abnormalities, and this enables cancer cells to acquire invasive behavior
  • Biological markers on a cancer cell identify it as abnormal, this may trigger the immune system to attack it, but more invasive cancers acquire more DNA mutations that can allow evasion of the immune system

In this article we will look at some aspects of cancer cells, what makes them different to ‘normal cells’. We’ll also look at the topics of stem cells, and cancer stem cells.

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Firstly it’s worth noting that there are characteristics that are common across all cancer types that are linked to the behavior of cancer cells2,3. However, different types of cancers have distinct characteristics, so a breast cancer cell is different to a leukemia cell, for example. The appearance and patterns of behavior of cancer cells are also variable. This is related to the stage of cancer, that is how far it has spread, and the grade, which describes the aggressiveness of a cancer. When medical specialists make decisions about cancer treatments, they take account of this information, which informs them on how the cancer might behave and how best to tackle it4.

Cell structure and cell division

Let’s look firstly at the basics of cells so we can then identify what makes cancer cells different to ‘normal’ healthy cells.  Living organisms are made up of cells. The cells in humans and other higher animals have a complex biological structure. Viewed with a powerful microscope, the cells from a human, a dog, or a chicken, have a more complex structure than bacterial cells, which have a more simple structure.

Inside most human cells is a control center, the nucleus, which can be visible as a dark body inside the cell. (Two types of blood cells – red blood cells and platelets – don’t have nuclei). There are also other bodies within cells that carry out functions including producing energy, disposing of waste and producing new building blocks for life.

The nucleus within the cell contains the cell ‘instruction book’ which is the genetic code, in the form of DNA. Apart from sperm cells and egg cells, all of a person’s cells will start out with the same DNA, which contains pairs of genes.

Cells divide to replace themselves. In healthy cells, the instructions encoded in the DNA are followed carefully and faithfully translated to produce a new pair of cells, by splitting the cell into two ‘daughter cells’. This starts with a process of DNA replication, to make a duplicate set of the pairs of all of the genes, then each set is sent to opposite sides of the cell. The cell then divides across the middle, to make two daughter cells. The pattern and pace of this cell replication is governed by an internal clock, the cell cycle clock, which is itself coded in the DNA.

Stem Cells

Stem cells are parent cells that arise in the very earliest stages of a growing embryo. Stem cells have the capacity to keep dividing and the flexibility to become different types of cells5. When they divide they can produce more stem cells or cells with a specialized function. Starting from the stem cell parent, if the cell divides to produce specialized cells, different genes will be switched on or off.  So when a stem cell divides to produce skin cells certain genes will be switched on to make them skin cells. The genes that are switched on enable different cells to carry out different functions. For example skin cells have a barrier function all over the body. Stem cells can keep replicating to renew a tissue through many generations of cells5.

Cancer cells versus healthy cells6

In this section, we’ll look at the difference between healthy ‘normal’ cells, and cancer cells. Healthy cells have three basic rules to follow, that cancer cells do not obey. Firstly, healthy cells only divide when there is the correct signal from the cell cycle clock. Secondly, healthy cells only divide a specific number of times, which differs between cell types and different body tissues. Thirdly, normal cells will self-destruct if they detect an abnormality that they cannot repair. This is because mistakes are frequently made in the cell replication process. These mistakes can cause the DNA to be changed, but the cell has intricate repair mechanisms that can detect and correct these mistakes or mutations in the DNA.

Damage to the DNA can also occur during the life of a cell due to carcinogens. However, if the damage to the DNA is significant the cell has a ‘suicide process’ (called apoptosis) that should be triggered to cause the cell to die, rather than allow the mutated DNA to be passed to another generation of cells.

These ‘housekeeping processes’ work to prevent many DNA abnormalities from persisting. However, as we shall see, some mutated cells do survive, and a cancer may develop because certain mistakes in the DNA can persist and the cell can then become transformed into a cancer cell7-9.

When a cell is transformed from a normal cell to a cancer cell, it doesn’t follow the rules of normal cell behavior. Firstly, cancer cells stop obeying the normal cell cycle clock, so the instructions that control normal cell division are ignored. Secondly, cancer cells keep dividing more than normal, this is why tumors expand within and beyond the tissue they arise in. Thirdly, cancer cells resist the requirement to self-destruct when an abnormality is detected. So cancer cells are effectively renegade cells that are failing to obey the rules of cell normality. These changes in behavior arise due to mutations in the DNA in the genes that govern cell behavior. Some of the changes in cell behavior are linked to changes in the structures and processes that manage the DNA, so-called epigenetic factors. Some mutations in the DNA that lead to cancer affect genes linked to cancer cell behavior, so-called oncogenes. In a normal cell these should stay silent, but in a cancer cell they may be switched on. Also ‘housekeeping’ genes that are involved in detecting and correcting DNA errors may be switched off. One area of cancer research is to study oncogenes and how they are controlled, and new treatments may arise from these studies.

"These ‘housekeeping processes’ work to prevent many DNA abnormalities from persisting"

Cancer stem cells

Cancer stem cells are another active area of cancer research that may lead to new treatments.   It is thought that some of the cells within tumours are cancer stem cells that have a capacity to keep dividing indefinitely10. Some studies suggest that cancer stem cells arise from damage to the DNA of healthy stem cells, and that they are the origin of cancers. It is also thought that when cancers come back after treatment it may be due to these persistent cancer stem cells that are then able to produce more cancer cells. Researching ways to kill cancer stem cells may provide new treatments that give lasting remission.

Cancer cell appearance and behavior

Cancer cells look different to healthy cells when examined with a microscope, they may have several nuclei, which can be swollen, as the cancer cell produces more DNA as part of its abnormal replication. Early stage, less aggressive cancers look and behave differently to more advanced, more aggressive cancers. Early localized cancers may progress as they acquire further mutations in the DNA of the cancer cells, acquiring new behaviors that enable them to become invasive and spread to other parts of the body6. Examining cancer tissue from a biopsy can indicate the aggressiveness of a cancer.

We have seen how cancer cells don’t behave like normal healthy cells. It is worth noting that there is a gradient of cell behavior from normal to cancer and some precancerous conditions involve early changes to cell behavior that can be corrected or reversed. For example, cervical smear tests (Pap smear) may detect enlarged cells that are not normal, but not yet cancer. Women affected by this cervical hyperplasia may, or may not, go on to develop cervical cancer11.

Cancer cell markers

In addition to looking different, and behaving differently, cancer cells have changes in their biological signature. Cell biologists study these biological signatures of cells, which include markers on the surface of the cell and within the cell, and substances produced by the cell. These cell markers identify cells to each other and are especially important for how the body’s immune system relates to different tissues in the body. Cell markers are encoded in the cell’s DNA, so when a cell becomes malignant the markers change, because of mutations in the DNA. The immune system can identify a cell as malignant and try to destroy it, this is how some early cancers are kept in check, but as more DNA mutations accumulate within a cancer cell it may acquire the ability to evade the immune system, and this leads to further cancer progression.

Sometimes these markers are detectable in the bloodstream, and doctors can use them to monitor disease activity and treatment. In other cases the marker is found from examining a biopsy of a tumor. Doctors and scientists can use these changes in the markers on cells to identify which treatments may work better to treat a particular cancer. Many new biological drugs work to target some cancer types because they have a specific change in key cell markers.

To summarize, cancer cells arise from healthy cells due to mutations in the DNA of the cell. If these mutations persist, the cell adopts different behavior. Cancer cells ignore the normal controls on cell division and keep dividing, and they ignore the ‘self-destruct’ process that should remove cells with abnormalities (called apoptosis). Cancer stem cells continue to produce more cancer cells, and even when a cancer has been removed, some cancer stem cells may persist and become a source of cancer recurrence. New ways to remove cancer stem cells may be part of a strategy to provide lasting cancer remission.

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