We're being graced with an official visit from Bob Weinberg
this week. One of the things he wanted to do was make an opportunity to meet a group of PhD students and other junior scientists. This strikes me as an excellent instinct because these vastly famous people doing their tours of honour will always have the chance to meet the other famous and important scientists at the host institution, and they will usually have a chance to be paraded for the general public, but it's quite easy for them to miss the actual working researchers. So, I signed myself up to be on the waiting list if there were any spaces for post-docs after the opportunity had been offered to the PhD students, and there were some extra spaces, so I attended the meeting yesterday. ( reactions )
One of the most exciting results in cancer biology recently is that the only cells that are capable of giving rise to tumours are adult stem cells. This means that cells that normally don't grow don't suddenly turn rogue and start growing all over the place, as used to be believed (recently enough that I was taught this model at university in the late 90s). But in fact, cancer happens when cells that normally do grow, ie stem cells, start making tumours instead of healthy tissues.
If you generalize from this, you start to wonder how far cancer cells are really normal cells in the wrong situations, rather than total aberrations. Bear in mind that all cells in the body contain exactly the same genes, but use a subset of them to perform their correct functions. Cancer cells probably have, oh, half a dozen mutations, genetic changes. But that might mean they have six altered letters out of three billion which are identical to those of normal cells. How do such tiny changes alter the whole function of the body, even fatally in many cases? What if these altered cells aren't something entirely new, they're just switching to the wrong sort of program.
There are two circumstances where cells are "supposed" to grow rapidly and relatively independently. One is when the embryo is developing, when it has only a few months to grow from a single cell one tenth of a mm wide, to a baby-sized baby 50 cm long (there are very few tumours that grow that fast!). The other is when a person is injured, and needs to rapidly make new tissue to repair the damage. Weinberg suggested that both these situations are relevant in a tumour.
So, we can argue that a tumour acts like a wound site
when there is no wound. It rapidly makes new blood vessels, which act to provide oxygen and nutrients to the centre of the tumour mass, but the blood vessels don't "know" that that is their "goal". The blood vessels start to grow because the body somehow "thinks" there is a wound there that needs to be repaired. The parts of the immune system which usually deal with wounds are all present at the sites of tumours; it was previously thought that this was a response to the presence of the "foreign" tumour, but in fact this doesn't make sense because the tumour isn't really foreign in the way that bacteria or other parasites are. So another way of looking at it is that the immune system, triggered inappropriately, actually causes
the tumour. The immune cells are responding to a wound that isn't there, so they send out chemicals which signal the tumour cells to grow, as they would normally signal new tissue to develop and repair an actual wound.
Weinberg also pointed out that this may mean that surgery is a really problematic way of dealing with cancer. You cut out the tumour, which obviously does need to happen. But. It's impossible to eliminate absolutely every cell, and even a single stem cell left behind can regenerate the whole tumour, because that's what stem cells do. Even worse, surgery causes an actual
wound, so all the immune system gubbins which is around will go into hyperdrive, making a really ideal environment for those stem cells to get going and grow like anything.
If this were the whole story, most cancers wouldn't be fatal. A tumour that does nothing except grow inexorably bigger is usually referred to as benign (this is a relative term, of course!) A malignant tumour is much more dangerous, for two reasons. Firstly, it actively invades the surrounding tissue, breaking down healthy tissue to make room for the tumour to grow. And secondly, pieces called metastases can break off and be carried round the body in the blood stream and lymph system, and cause new tumours all over the place. These metastatic tumours often can't be removed by surgery as there are too many of them, and it's often only a matter of time before they get into vital organs and cause a total system failure, otherwise known as death.
But there are some normal cells that are meant to invade the surrounding tissue, and meant to be able to move around the body and start growth at new sites. Namely, the cells of the early embryo. Weinberg's theory is that malignant cells turn on genes that are normally turned on at the moment when the blastocyst, the ball of frog-spawn like cells, starts to turn into an actual embryo with recognizable features. These genes help the cells to move around to position themselves in the right places to form specialized tissues, and also to invade other parts of the embryo and mother's uterus as necessary. So if these genes get turned on in an adult, you can get metastatic cells.
This feels like it could be a really productive novel way of looking at cancer. And I think it's cool!