If a cancer cell is immortal, then why does it not make the human immortal?

Cancer cells are immortal only in a very specific sense. Normal human cell lines can only divide a certain number of times (roughly 40–70 times). The maximum number of divisions for a cell line is called its Hayflick limit.

Each time a cell divides, when the chromosomes are being copied, a small piece breaks off the ends of the chromosomes. At the end of each chromosome there is a long section of repetitive DNA, called the telomere. This region doesn't code for anything. It's just there, like a cap, to protect the rest of the chromosome during replication. When the telomeres are gone, the replication process starts to eat into the coding regions of the chromosomes. This is very, very bad: it causes huge numbers of mutations, and makes chromosomes likely to fuse with each other.

But it normally doesn't happen, because when the telomeres get too short for the chromosomes to replicate safely, the cell senesces. Senescence, for a cell, means that it transforms into a different state, one where it may survive a long time, and go on performing its usual functions, but will never again divide. Eventually, it will die childless.

Now, you're probably asking yourself - if every DNA replication damages the chromosomes, how can cell lines have survived since the origin of life? And the answer is, chromosomes can actually repair themselves. To do this, most animals, humans included, use an enzyme called telomerase, which lengthens the telomeres.

The gene for telomerase is active in human stem cells during early development, which means the Hayflick limit doesn't apply to them. We need this gene - otherwise, all our cell lines would be doomed.

But we also need the Hayflick limit. If we let our cell lines go on dividing indefinitely, they will be subject to natural selection inside our bodies - that is, they will evolve to replicate faster and faster, and take more and more resources from our bodies. In other words, the Hayflick limit is a primary defense against cancer. So in most older tissues, the gene for telomerase is deactivated by methylation.

If a cell line, through mutations, loses the machinery that allows it to senesce in a normal, dignified fashion, it will instead go into a crisis state as it approaches the Hayflick limit. It starts to suffer massive numbers of mutations. These trigger internal policing mechanisms (such as p53), which usually cause the cell to immediately commit suicide.

But what if those policing mechanisms are also mutated? Then the cell may fail to commit suicide, and go on dividing even after its telomeres are destroyed, though it will still face a huge mutation rate.

One of the things that happens during cancer evolution is that regulation of methylation gets disrupted. Large parts of the genome are stripped of their methyl groups. This allows deactivated genes such as telomerase to become functional again.

Again, mostly, this makes a horrible mess of the genome, which either triggers suicide or simply makes the cell incapable of survival. But you only need one survivor to found a new population. So, during cancer evolution, the gene for telomerase is commonly re-awakened, allowing the chromosomes to repair themselves, and thus safely bypass the Hayflick limit. This is what is meant by ‘immortality' in cancer cells: they are not subject to the normal lifespan of human cell lines.

Unfortunately, it is this very property that allows them to out-compete our healthy tissues, growing boundlessly, consuming energy and nutrients, and blocking our organs from functioning. Cancer cells are doomed individualists: they agree with Dylan Thomas:

Do not go gentle into that good night,
Old age should burn and rave at close of day;
Rage, rage against the dying of the light.

Though wise men at their end know dark is right,
Because their words had forked no lightning they
Do not go gentle into that good night.

There are only a few recorded cases where the immortality of cancer cell lines has translated into anything like functional immortality: for the cell lines, that is, not for the bodies that once hosted them. One is HeLa, a cell line cultured from the cervical cancer of Henrietta Lacks (without consent), now used extremely widely in research. Another is an 11,000 year old dog cell line, which managed to evolve into a transmissible venereal disease. A third type, Tasmanian devil facial tumors, appeared in the 1990s, and is transmitted by biting, a popular behavior in both hostile and amorous encounters among devils. The devils have been driven close to extinction by this disease, though there are reports that they are starting to fight back.

Henrietta Lacks' ‘Immortal' Cells

Transmissible [corrected] dog cancer genome reveals the origin and history of an ancient cell lineage.

Tasmanian devil facial tumour disease (DFTD)

http://www.nature.com/articles/n...


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