Why do some cancer cells divide not into two, as cells are supposed to do in mitosis, but into three-four new cells that look thoroughly abnormal? This question was raised as early as the 1890s by the German tumor researcher David Hansemann, who could observe the strange mitosis even using the microscopes of his day. Now another David, Lund University researcher David Gisselsson, has found an answer.
Together with associates from the Section for Clinical Genetics, David Gisselsson has long been studying chromosome changes in various sorts of cancer cells. Contrary to the earlier belief that tumor cells are rather stable genetically, a few years ago he was able to show that genetic chaos prevails in certain severe cancer forms.
"The normal number of chromosomes in a human cell is 46. But in tumors from skeletal and pancreatic cancer, some cells can have far fewer than 46 chromosomes while others have several hundred. The structure of these chromosomes is also often abnormal-for example, they have lost some parts, traded segments with each other, and copied certain genes in mass production," says David Gisselsson.
The Lund scientists have scrutinized these phenomena in a series of studies. They have been able to demonstrate that certain tumor cells get stuck in mitosis, so that their chromosomes do not divide neatly in two directions, but rather get pulled apart in a disorganized manner into the daughter cells. This is because the ends of the chromosomes, the so-called telomers, have lost their protective exteriors.
Cells with truncated, unprotected telomers from different chromosomes actually ought to simply die, but this does not happen in these tumor cells. Instead, the naked telomers cling to each other. This can be the explanation for the abnormal number of chromosomes in some tumor cells, where certain ones have incorporated a number of extra chromosomes while others wind up with too few.
Having the wrong number of chromosomes does not lead directly to death in these tumor cells. On the other hand, they have problems with mitosis.
"We have observed that these cells sometimes try to divide, but they fail and go into an idle state. If they then try again, they tend to divide in three or four directions. This explains Hansemann's discovery from the 1890s!" says David Gisselsson.
In its latest study the Lund team has also shown that the daughter cells of those cells which divide in more than two directions have a completely random distribution of chromosomes. This genetic chaos is so great that the cells usually die.
Research groups in several countries have been studying von Hansemann mitosis at the molecular level, that is, what happens inside the cell. But this work has proven to have little relevance to the struggle against cancer. These are not the cells that make a tumor grow, since they themselves typically die off.
On the other hand, the Lund team now wishes to study substances that might be able to counteract cancer by further damaging already truncated telomers. In that way it may be possible to increase the genetic chaos in tumor cells in order to get more of them to simply die.