While cancer is one of the biggest Western killers, when considered on a "per cell" basis, it remains rare. One of the biggest complications resulting from cancer, other than the disease itself, is its ability to spread, or metastasise. Again, this spread is far from unheard of, but in actual fact, metastasis is inefficient.
The anatomical viewpoint suggests that the spread of cancer follows the routes available for the passage and growth of cells:
- through blood vessels/lympathic ducts (=permeation)
- along fascial (connective tissue) planes
- immediate intercellular invasion (=infiltration)
- through ducts of sweat glands or hollow body organs (viscera)
- direct seeding in body cavities (e.g. an 'ascites' tumour grows suspended within a cavity)
If the anatomical viewpoint alone were responsible for the pattern of metastasis, then organ involvement would reflect the proportion of cardiac output (the volume of blood pumped by the heart per minute) it received. In light of this argument, the anatomical viewpoint is not a sufficient explanation for the spread of cancerous cells.
The seed and soil view also takes into consideration the production of growth factors by target tissues and resultant specific interactions between cancer cells and body tissues. This seems a sensible explanation for the preference of various types of cancer cells for specific tissues.
If labelled malignant tumour cells are injected into an experimental animal, the initial sites they lodge at are quite distinct from the sites of development of secondary tumours.
Cancer cells must:
- overcome adhesion at initial site
- travel to the site of invasion along routes mentioned above, and survive and remain tumorogenic during transit
- adhere to new sites, with the help of adhesion molecules (e.g. ICAMs)
The disruption of this adhesion is of clinical interest, and has recently made the news. However, limiting adhesion also reduces the recruitment of immunological cells. Susceptibility to infection is increased in cancer; limiting leucocyte recruitment may have hazardous consequences. Furthermore, reducing adhesion may increase the likelihood of the occurence of metastasis.
- multiply at the site, supported by the production of growth factors by the target tissue
- escape demise at the hands of the immune system.
This final point is common to cancer and pregnancy. The foetus is a chimera, expressing both maternal genes and paternal genes which should be recognised as foreign by the mother's immune system. They're not.
Why? Possibly due to the expression of a molecule named 5T4, found on embryonic stems cells (ESCs), particularly the cells of the trophoblast - a placental layer. The 5T4 molecule is responsible for imparting motility to stem cells, allowing them to relocate (metastasise) to a new site. In adult cancerous cells, 5T4 is overexpressed. In normal cells, it is expressed at very low levels.
A new approach to cancer therapy is the administration of a vaccine which causes the body to launch an immune response to 5T4. Human clinical trials have proved succesful. A new "magic bullet" therapy is also under development, which involves a dose of antibodies to latch on to, and render ineffective 5T4.
It is unlikely the trials involved pregnant women, and even more unlikely (rightly so) that an ethical committee would allow such a trial. But what about subsequent pregnancies? Although IgG is the only antibody capable of crossing the placenta and entering foetal blood, any such antibodies against 5T4 could have catastrophic effects on a developing foetus. Consequences on foetal health seem to have escaped mention, but there is nothing to say the effects on pregnancy have been evaluated. If indeed no such investigation has taken place, the hype over the new found treatment may itself be premature.
