What are cancer cells?

Cancer cells are the type of cells that have defects in the control mechanisms that govern how often they divide, and in the feedback systems that regulate these control mechanisms (i.e. defects in homeostasis). Hence they uncontrollably divide, resulting in the cause of benign or malignant tumours.

What’s the difference between normal cells and cancer cells?

Normal cells grow and divide, but have many controls on that growth. They only grow when stimulated by growth factors. If they are damaged, a molecular brake stops them from dividing until they are repaired. If they can't be repaired, they commit programmed cell death (apoptosis). They can only divide a limited number of times. They are part of a tissue structure and remain where they belong. They need a blood supply to grow.

All these mechanisms must be overcome in order for a cell to develop into cancer. Each mechanism is controlled by several proteins. A critical protein must malfunction in each of those mechanisms. These proteins become non-functional or malfunctioning when the DNA sequence of their genes is damaged through acquired or somatic mutations(mutations that are not inherited but occur after conception). This occurs in a series of steps, which Hanahan and Weinberg refer to as hallmarks.

What are the properties of cancer cells?

1. Self-sufficiency in growth signals

Cancer cells do not need stimulation from external signals (in the form of growth factors) to multiply.

Typically, cells of the body require hormones and other molecules that act as signals for them to grow and divide. Cancer cells, however, have the ability to grow without these external signals. There are multiple ways in which cancer cells can do this: by producing these signals themselves, known as autocrine signalling; by permanently activating the signalling pathways that respond to these signals; or by destroying 'off switches' that prevent excessive growth from these signals (negative feedback).

2. Insensitivity to anti-growth signals

Cancer cells are generally resistant to growth-preventing signals from their neighbours.

To control cell division, cells have processes within them that prevent cell growth and division. These processes are orchestrated by proteins known as tumor suppressor genes. These genes take information from the cell to ensure that it is ready to divide and will halt division if not (when the DNA is damaged, for example).

In cancer, these tumour suppressor proteins are altered so that they don't effectively prevent cell division, even when the cell has severe abnormalities. Another way cells prevent over-division is that normal cells will also stop dividing when the cells fill up the space they are in and touch other cells; known as contact inhibition. Cancer cells do not have contact inhibition, and so will continue to grow and divide, regardless of their surroundings.

3. Evading programmed cell death or Activating Invasion and Metastasis

Apoptosis is a form of programmed cell death (cell suicide), the mechanism by which cells are programmed to die in the event they become damaged. Cancer cells are characteristically able to bypass this mechanism.

Cells have the ability to 'self-destruct'; a process known as apoptosis. This is required for organisms to grow and develop properly, for maintaining the tissues of the body, and is also initiated when a cell is damaged or infected. Cancer cells, however, lose this ability; even though cells may become grossly abnormal, they do not apoptosis. The cancer cells may do this by altering the mechanisms that detect the damage or abnormalities. This means that proper signalling cannot occur, thus apoptosis cannot activate. They may also have defects in the downstream signalling itself or the proteins involved in apoptosis, each of which will also prevent proper apoptosis.

4. Limitless replicative potential

Non-cancer cells die after a certain number of divisions. Cancer cells escape this limit and are apparently capable of indefinite growth and division (immortality). But those immortal cells have damaged chromosomes, which can become cancerous.

Cells of the body have a limited number of divisions before the cells become unable to divide (senescence), or die (crisis). The cause of these barriers is primarily due to the DNA at the end of chromosomes, known as telomeres. Telomeric DNA shortens with every cell division, until it becomes so short it activates senescence, so the cell stops dividing. Cancer cells bypass this barrier by manipulating enzymes that increase the length of telomeres. Thus, they can divide indefinitely, without initiating senescence. Mammalian cells have an intrinsic program, the Hayflick limit, that limits their multiplication to about 60–70 doublings, at which point they reach a stage of senescence.

This limit can be overcome by disabling their pRB and p53 tumor suppressor proteins, which allows them to continue doubling until they reach a stage called crisis, with apoptosis

The counting device for cell doublings is the telomere, which decreases in size (loses nucleotides at the ends of chromosomes) during each cell cycle. About 85% of cancers upregulate telomerase to extend their telomeres and the remaining 15% use a method called the Alternative Lengthening of Telomere.

5. Sustained angiogenesis

Angiogenesis is the process by which new blood vessels are formed. Cancer cells appear to be able to kickstart this process, ensuring that such cells receive a continual supply of oxygen and other nutrients.

Normal tissues of the body have blood vessels running through them that deliver oxygen from the lungs. Cells must be close to the blood vessels to get enough oxygen for them to survive. New blood vessels are formed during the development of embryos, during wound repair and during the female reproductive cycle.

An expanding tumour requires new blood vessels to deliver adequate oxygen to the cancer cells, and thus cancer cells acquire the ability to orchestrate the production of new vasculature by activating the 'angiogenic switch'. In doing so, they control non-cancerous cells that are present in the tumour that can form blood vessels by reducing the production of factors that inhibit blood vessel production and increasing the production of factors that promote blood vessel formation.

6. Tissue invasion and metastasis

Cancer cells can break away from their site or organ of origin to invade surrounding tissue and spread (metastasize) to distant body parts.

One of the most well-known properties of cancer cells is their ability to invade neighbouring tissues. Dictates whether the tumour is benign or malignant, and is the reason for its dissemination around the body. The cancer cells have to undergo a multitude of changes in order for them to acquire the ability to metastasize. It is a multistep process that starts with a local invasion of the cells into the surrounding tissues.

7. Deregulated metabolism

Most cancer cells use abnormal metabolic pathways to generate energy. Cancer cells exhibiting the Warburg effect upregulate glycolysis and lactic acid fermentation in the cytosol and prevent mitochondria from completing normal aerobic respiration (oxidation of pyruvate, the citric acid cycle, and the electron transport chain).

Instead of completely oxidizing glucose to produce as much ATP as possible, cancer cells would rather convert pyruvate into the building blocks for more cells. In fact, the low ATP:ADP ratio caused by this effect likely contributes to the deactivation of mitochondria. Mitochondrial membrane potential is hyperpolarized to prevent voltage-sensitive permeability transition pores (PTP) from triggering of apoptosis

8. Evading the immune system

Despite cancer cells causing increased inflammation and angiogenesis, they also appear to be able to avoid interaction with the body via a loss of the interleukin-33 immune system.

9. Genome instability

Cancer cells generally have severe chromosomal abnormalities which worsen as the disease progresses. HeLa cells, for example, are extremely prolific and have tetraploidy 12, trisomy 6, 8, and 17, and a modal chromosome number of 82 (rather than the normal diploid number of 46). Small genetic mutations are most likely what begin tumorigenesis, but once cells begin the breakage-fusion-bridge (BFB) cycle, they are able to mutate at much faster rates.

10. Inflammation

Recent discoveries have highlighted the role of local chronic inflammation in inducing many types of cancer. Inflammation leads to angiogenesis and more of an immune response. The degradation of extracellular matrix necessary to form new blood vessels increases the odds of metastasis.