What are the hallmarks that are common to all cancers?
There are six distinctive hallmarks which are common to all cancers, regardless of type. They are demonstrated in the Smart Art Graphic below. For more information regarding types of cancers, you can find the information at Benign Tumours vs. Malignant Cancers.
How do cancer cells arise in the first place?
Cancer cells tend to arise as a result of a process known as carcinogenesis. This happens at both the genetic level and at the cellular level, and is caused by genetic mutations. There are usually many different types of cells present in tumours by the time they are detected, despite the fact that many tumours arise from one cell becoming abnormal. By discussing the six hallmarks that I mentioned above, I’ll be mentioning in more detail how cancers are able to differ from normal cells and can become so detrimental to the human body.
Invasion and Metastasis
This is a long topic to go over, so I’ll discuss this separately in the page Invasion and Metastasis.
Independent Production of Growth Factors
All cells require growth factors in order to increase in size and divide into greater numbers. They tend to get stimulation by growth hormones by receiving signals from neighbouring cells, otherwise known as paracrine action. The difference between normal and cancer cells is that whilst normal cells are interconnected, cancer cells become relatively independent because they gain the ability to produce their own growth factors. Additionally, cancer cells tend not to receive signals from neighbours: rather, they tend to activate themselves via the autocrine loop.
What are proto-oncogenes and oncogenes?
Proto-oncogenes are normal genes within a cell. When they are exposed to mutagens such as asbestos, arsenic or ionic radiation, they can become mutated and potentially lead to the production of tumours: these mutated genes are known as oncogenes. The most commonly known mutated proto-oncogene is known as RAS: it tends to appear in approximately one third of the cases of tumours which are detected. Another well-known example is the ABL proto-oncogene. This particular proto-oncogene promotes apoptosis, and when it is mutated, it produces chronic myeloid leukaemia when combined with the BCL gene.
Lack of Sensitivity to Anti-Growth Signals
You may have heard of Newton’s third law of motion, which states that ‘every action has an equal and opposite reaction.’ This theory can also apply to both oncogenes and growth inhibitory signals. The oncogenes accelerate cell growth and cell division and the growth inhibitory signals put on the brakes. The production of growth inhibitory signals is controlled by means of tumour suppressor genes. In every cell, there are two copies of tumour suppressor genes and the normal gene has dominant expression over the mutated gene.
Hang on… if the normal gene is dominant over the recessive gene, how does cancer appear?
Before I discuss that, I might as well go over some biology to clear some things up…
As the picture alongside demonstrates, in humans, every cell contains 23 pairs of chromosomes: 22 pairs of autosomal chromosomes and either 2 X chromosomes (in females) or 1 X and 1 Y chromosome (in males). The autosomal chromosomes are often talked about when scientists refer to dominant and recessive traits. They are responsible for many of our features, from the colour of our eyes to the presence of a ‘hitchhiker’s thumb’. Some of the traits are Mendelian in nature and so therefore can be tracked in a laboratory setting, whereas others are more random. For now, just to keep things simple, I’ll only refer to Mendelian traits.
For a trait to be autosomal dominant there must be at least one copy present in order for the trait to present itself: it can either be heterozygous (one dominant and one recessive, often written Aa) or homozygous (both dominant copies present, often written AA).
For an autosomal recessive trait to be present, only copies of the recessive gene must be present (is therefore considered homozygous recessive, and written aa). Under most circumstances, there is nothing wrong with having autosomal recessive traits: it means that you may have brown or green eyes instead of blue eyes and you wouldn’t have a hitchhiker’s thumb (both blue eyes and thumb type are determined by dominant Mendelian traits) However, these genes can also be diseased in nature. In order for cancer to appear, both of the normal gene types need to be ‘knocked out’. This is done by either genetics (i.e. the parent passing the genetic fault to the child), or by exposure to mutagens. I’ll discuss mutagens further in Danger: Mutagens Cause Cancer!
Limitless Replicative Potential
Normal cells have a limited lifespan. They are capable of dividing up to 70 times before entering senescence, which is defined as a permanent stoppage of the cell cycle which allows the cells to divide. As the picture alongside shows, the structures known as telomeres are present on the ends of each chromosome: in normal cells, these telomeres shorten as the cells become older, and are part of the reason that we humans are mortal creatures. However, cancer cells are capable of maintaining the length of their chromosomes by the use of the enzyme telomerase. In a sense, keeping the telomeres long makes the cells become ‘immortal’.
Another difference between normal and cancer cells is that normal cells are kept under strict codes of growth as well as senescence and eventual death. The major law enforcer of cells is the gene known as p53. I’ll be discussing this gene further in p53: Cell Police Force. In a sense, cancer cells are criminals because they have no regard for the laws that p53 impose, and as a consequence, they grow uncontrollably and wreak havoc on the body.
Angiogenesis is defined as the creation of new blood vessels. This process is necessary for malignant tumours to develop and metastasize because like almost all other cells in the body, they require oxygen and nutrients to be taken in and wastes to be removed. The loss of the p53 gene is tied to the ability of the tumour cells to be able to create their own blood vessels, because p53 can produce thrombospondin-1, which inhibits angiogenesis. More information regarding the role of angiogenesis can be found in Invasion and Metastasis.
As strange as it sounds, angiogenesis is dependent on the balance between factors which stimulate angiogenesis and factors that inhibit angiogenesis. The process of angiogenesis generally does not occur until the tumour has been around for a matter of years, when the angiogenic switch is turned on. Angiogenic factors are produced in one of two ways: either by the cells themselves, or by inflammatory cells. Hypoxia (lack of oxygen) is a major stimuli for angiogenesis: this environment triggers the production of hypoxia-induced factor 1-alpha (HIF1α).