Properties of Transformed Cells Flashcards
Why is proliferation regulated on an organismal scale?
Cell multiplication is carefully regulated to respond to the needs of tissue’s and whole organism’s growth requirements.
This is particularly true of young animals; whose cell division is on the whole largely upregulated to increase body mass.
In an adult, cell division and death must be finely balanced to maintain a steady state, except in proliferating tissues or in response to certain stimuli.
How does the rate of proliferation vary between cell types? give examples.
Different cell types in the body multiply at different rates:
- WBCs proliferate extremely quickly in response to infection
- Intestinal cells possess centres of proliferation, replacing the cells that live for only a few days before sloughing off
- Red blood cells have a half-life of around 100 days, and must be replaced by haematopoiesis
- Healthy hepatocytes very rarely die
- Brain cells die slowly with even less replacement
How is proliferative misregulation self-perpeutating?
When a cell acquires a mutation that either inhibits apoptosis or stimulates proliferation, it begins to out-multiply the other cells in the tissue.
Due to the increased rate of proliferation and the inherent genomic instability associated with such mutations, one of these cells is likely to acquire a further mutation that increases survival.
Once again the descendants of this cell will become the most populous, and this will continue as natural selection selects for the most dangerous cells, and cell proliferation rate increases until a tumour forms. This process is called clonal expansion.`
How does tumour size change during clonal expansion and what implication does this have on treatment?
It takes a large number of doublings to produce a tumour visible on an X-Ray scan, and even more to produce one that is palpable.
Due to the exponential nature of the population increase of proliferating cells, it is not long after visibility that the tumour is large enough to kill the host. Hence the window between when cancer can be diagnosed and when it becomes lethal is inconveniently small.
What is the difference between benign and malignant tumours?
Benign tumours are those who do not metastasise to other parts of the body, as opposed to malignant ones which do.
> 90% of mortality from cancer is attributable to metastases
What makes benign tumours safer?
Benign tumours are localised and non-invasive, and include such growths as adenomas and warts, and are surrounded by a fibrous capsule that prevents the escape of the cells inside of it. This allows them to be easily excised and so cured.
How can benign tumours be dangerous?
‘Benign’ tumours can still cause sickness and even death by just their steric presence – which may cut off blood flow, disrupt tissue/organ flow or prevent proper CNS function.
Another possibility is the development of a hormonal tumour, which despite the massive proliferation retains its original function as a gland, leading to massive over production of hormones (or other biologically active substances) and subsequent endocrine havoc.
What makes tumours capable of metastasising?
The ability of a tumour to metastasize is predicated upon their ability to break the cell-cell contact with their surrounding tissue, and to breach the basal lamina which underlies epithelial cell layers and the endothelium of blood vessels.
What is the seed and soil theory?
Malignant tumours are made so by their ability to breach the basement membrane of the tissue in which they reside, allowing ‘seed cells’ to enter the bloodstream and settle in distant hospitable tissues (the seed and soil theory).
How does the phenotype of metastatic tumours differ from benign ones?
Malignant tumour cells tend to be less differentiated than benign ones, though their phenotype can vary with time due to tumour evolution/genotypic variability. Some of the most genomically unstable cells in aggressive tumours can have chromosomal abnormalities.
What challenges are faced by metastisising tumours?
Cancer cells undergoing metastasis are unlikely to survive the transit through the bloodstream, less than 0.1% are able to settle somewhere before being destroyed.
Why is it difficult for metastisising cells to survive in the bloodstream and how can this be exploited?
This is in part due to the immune system, which due to the changes in the make-up of the cell surface can recognise cancer cells and destroy them through use of natural killer cells. This allows antibodies raised against the cancer cells to sometimes be effective treatments.
Where are metastasising cells likely to be deposited?
The cells are more likely to be deposited in some places than others, especially in the lungs due to the thin capillaries and low blood pressure favouring adherence to the blood vessel wall and subsequent escape into the surrounding tissue to form a micrometastasis.
Why might metastases be different to their parent tumour?
The tumours these grow into (termed metastases) are often very different to the primary tumours in many ways, due to the different hormonal environment in which the tumour has grown and evolved.
What does the difference in phenotype between cancerous and other cells allow for?
Cancer cells tend to have distinctive visible differences, allowing for easy microscopy diagnosis of cancer from simple biopsies such as pap smears – a very useful technique for determining whether a cancer is invasive.
