How do cancer cells arise


The concepts behind ‘how do cancer cells arise’ have been taken from Professor Jane Plant’s famous book, Prostate Cancer – understand, prevent and overcome, as I had loved it the first time I read it in 2009  and thought it would be great to share the basic reasons why cancer cells come out of nothing.

Cells Behaving Badly

In order to understand why cancer is so hard to treat and cure, we need to look at it in a bit more detail and to acquire some basic information.

WHEN BAD THINGS HAPPEN TO GOOD CELLS

As you probably know, your body is made of millions of millions of cells living in complex interrelationships with each other. Normally, your cells do not grow out of control, they do not invade each other’s territory, and cells from, say, the lining of your intestines or parts of your prostate gland do not take off and start growing in other organs such as your bones or liver, a process called metastasis. But, as indicated above, it is the property of cancer cells to do precisely these three things that makes them so dangerous.

Even when cancer cells are removed from the human body and grown in a laboratory culture, they behave very differently from normal cells. For example, normal cells are fussy about the nutrients they consume, but cancer cells are not. Also, normal cells reproduce only until they touch each other, and then they stop (a phenomenon known as contact inhibition).  By contrast, cancer cells keep on propagating and will pile up in mounds because they produce a substance called telomerase which stops them from counting how many times they have reproduced themselves.

Telomerase is an enzyme that regulates the length of chromosomes in higher organisms, known as telomeres. In most human cells, the activity of telomerase is suppressed, and telomeres shorten progressively with each cell division. By contrast, 80-90 per cent of human cancers have been found to have active telomerase, resulting in continued cell proliferation.

So why do cancer cells start behaving badly? Why do they grow out of control and eventually, if unchecked, start migrating across the body, establishing secondary tumours? To understand why, you need first to be aware of the simple fact that your body must make new cells when necessary- and in some tissues ‘necessary’ is, in fact, almost constantly. As your body ‘wears out’, new cells are created to replace older, dead or damaged ones. This process is called cell division or, more technically, mitosis.

When cells reach a certain critical size and metabolic state, they divide and create new daughter cells.  The daughter cell inherits an exact replica of the hereditary information (an exact replica of the types of genes in an exact sequence) of the parent cell. Not all cells divide at the same rate. For example, liver cells in the adult do not normally divide, but they can be stimulated to do so if part of the liver is removed surgically. On the other hand, the stem cells in human bone marrow are a good example of cells that divide rapidly and almost constantly. The average red blood cell lives only about 120 days. There are about 2.5 trillion of them in an adult body. To maintain this number, about 2.5 million new red blood cells must be produced every second. In total, about 2 trillion cell divisions occur in an adult human every 24 hours; that’s about 25 million a second!

Normally, the cells in your body reproduce only when instructed or allowed to do so by the cells around them, according to a complex and highly evolved system, which maintains the size and shape of your body throughout your life.  Hence, your ears and eyes, feet and legs stay in proportion to the rest of your body.

Now you can begin to imagine what would happen if this process goes wrong. If something happens to increase the rate at which one group of cells reproduce, the result will be an ever-increasing number of cells that have no beneficial function to the body, yet are absorbing nutrition at an increasing rate. And that is what a tumour is. If the cells remain in their place of origin and do not directly invade surrounding tissues, the tumour is said to be benign (or non-cancerous). If the cells invade neighbouring tissues and cause distant secondary growths (metastases), the tumour is known as malignant. Hippocrates called this abnormal cell process ‘karkinos’, literally meaning ‘crab’, from which the modern word ‘cancer’ is derived.

THE WRONG KNITTING PATTERN

How can this process go wrong?  Well, it is all a matter of control. Cell division (mitosis) happens according to a well-established cycle. First, the cells increase in size and make new proteins before a resting phase; then they make two exact copies of the cell chromosomes.

Chromosomes are the strings of DNA that contain our gene sequence and they carry all the instructions about how to make us: blue eyes, curly hair, and so on.

Next, the chromosomes line up and finally they divide into two. The whole process is designed to make new cells that are exact copies of the ones they are replacing. This sequence of events is controlled by the cell’s genes.

Each cell in the human body contains tens of thousands of genes which provide detailed instructions that determine not only the colour of our eyes or hair, but also instructions about cell division, growth and death. Genes can be thought of as knitting patterns or computer programs which, in the case of cancer cells, have somehow had a few mistakes introduced. Just think how a sweater would turn out of it was made from a pattern with a mistake in it. It’s the same idea.

Most cells, no matter what their shape or function, have an outer surface – the cell membrane -inside which is a thick fluid called cytoplasm. Then, with the exception of red blood cells, all cells have a ‘control centre’, called a cell nucleus. In the cell nucleus are the chromosomes, made of strands of a special substance called DNA that contains our genes. The genes specify how to make particular proteins that carry out their work. When a gene is activated it causes such proteins to be made. Mutations (mistakes in genes) can cause the wrong amounts or types of the protein to be produced, thus sending the wrong message. Then, when the cell begins its cycle of mitosis, there are errors – just like the misshapen sweater made from the misprinted knitting pattern.

All cells, including prostate cells, have receptors for chemical messengers such as hormones and immunity and growth factors. Receptors are special parts of the cell designed to allow chemical messengers such as particular hormones or growth factors to ‘dock’ and deliver their messages. In the case of growth factors, for example, one end of each receptor protrudes into the fluid between the cells, the other end projects into the cell’s cytoplasm and in this way creates a conduit along which the message starts to be transmitted. So, for example, when a growth factor docks on to an appropriate receptor its message is passed directly into the cytoplasm. There it begins the relay of a message that is carried from one protein to the next until it reaches the cell nucleus. This relay occurs along what is sometimes called a pathway. Once in the cell nucleus, the message activates genes to initiate their instructions – in this case, for the cell to begin its growth cycle. But cells can receive other messages as well.

Types of Genes in Normal Cells

There are basically three types of genes in normal cells that can go wrong to produce cancer: those that say ‘grow’, called proto-oncogenes by doctors and researchers; those that say ‘don’t grow’, called tumour-suppressor genes; and those that say ‘fix it’, instructing the cell to repair damage or, in extreme situations, self-destruct, called apoptotic genes.

Courtesy of The book by Professor Jane Plant, Prostate Cancer – understand, prevent and overcome

Currently, most doctors think that the cells in cancer are descended from a common ancestral cell that at some point in time – probably years before any tumour is detected – initiated a programme of inappropriate reproduction. Somehow one or more of the knitting patterns for the ‘grow’, ‘don’t grow’ and ‘fix it’ genes crucial to cell mitosis accumulated a series of mistakes resulting in the ancestral cancer cell. Normally, the body has a complex ‘quality control’ system to ensure that such errors are detected and eliminated – to the extent of causing damaged cells to self-destruct (the cell’s ability to commit suicide, ‘apoptosis’). But somehow, the ancestral cancer cell avoided the body’s quality-control safeguards and began to grow out of control. Normal DNA repair mechanisms didn’t work and, for some reason, the body’s immune system didn’t recognize the cancer cells as abnormal and so failed to kill them off. Even the ‘final solution’ of cell suicide failed to work. You can see from this sequence of events that cancer is actually the result of a series of failures, starting from mistakes in the cell’s genes – the knitting patterns.

These mistakes in the genes are called mutations, and most cancers possess mutations in one or more of the three gene categories. The progression of cancers from an individual damaged cell to a cluster of damaged cells, then to non-aggressive cancer and finally to a highly aggressive cancer is generally considered to result from the continued accumulation of mutations. Cells from advanced cancer typically have many genetic changes and chromosome rearrangements, although these are considered to be the result rather than the cause of malignancy.  The number of mutations required for the development of cancer varies with the cancer type.

The first genes that go wrong are the ‘grow’ genes, the genes which produce normal growth proteins in our cells, which relay signals to the nucleus (the control centre of the cell), stimulating growth in response to proteins and other substances in the intercellular fluid. The signaling process involves a series of steps which begin at receptors on the cell membrane (or within the cell, in case of steroid hormones), then involve a host of intermediary proteins in the cell cytoplasm and end with the activation of factors in the cell nucleus which help to move it through its cycle of growth and replication.

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