Brussels, 07 Sep 2005
Scientists at the European Molecular Biology Laboratory (EMBL) in Heidelberg and the Institute of Biomedical Research of the Parc Científic de Barcelona (IRB-PCB) have now added key evidence to claims that some types of cancer originate with defects in stem cells. In a study, reported this week in the on-line edition of Nature Genetics, they show that if key molecules aren't placed in the right locations within stem cells before they divide, deadly tumours can result.
Cells in the very early embryo are interchangeable and undergo rapid division. Soon, however, they begin differentiating into more specific types, finally becoming specialized cells like neurons, blood, or muscle. As they differentiate, they should stop dividing and usually become an integral part of specific tissues. Some tumour cells are more like stem cells, in the sense that they are identical, they divide quickly and, in the worst case, can metastasise - spreading throughout the body and implanting themselves in new tissues.
As specialised cells may die naturally through age or injuries, the body keeps stocks of stem cells on hand to generate replacements. Usually the stem cell divides into two types: one that is just like the parent, which will be kept to maintain the stock, and another that differentiates. This is what happens with neuroblasts: cell division creates one large neuroblast and a smaller cell that can become part of a nerve. This process is controlled by events that happen prior to division: the parent cell becomes asymmetrical and collects a set of special molecules, including Prospero and other proteins, in the area that will become the specialised cell.
'This asymmetry provides the new cell with molecules it needs to launch new genetic programs that tell it what to become,' says Cayetano González, whose group began the project at EMBL and has continued the work as they moved to the IRB-PCB. 'The current study investigates what happens when the process of localising these molecules is disturbed.'
Whether Prospero and its partners get to the right place depends on the activity of specific genes in the stem cell. Emmanuel Caussinus, an EMBL PhD student from González's group and co-author of the article, succeed in creating neuroblasts in which these genes were disrupted. 'We no longer had normal neuroblasts and daughter cells capable of becoming part of a nerve,' Caussinus says. 'Instead, we had a tumour.' When these altered cells were transplanted into flies, the results were swift and dramatic. The tissue containing the altered cells grew to 100 times its initial size; cells invaded other tissues, and death followed. According to Caussinus, the growing tumour became 'immortal', and cells could be re-transplanted into new hosts for years, generation after generation, with similar effects.
The study proves that specific genes in stem cells - those which control the fates of daughter cells - are crucial. If such genes are disrupted, the new cells may no longer be able to control their reproduction, and this could lead to cancer. 'It puts the focus on the events that create asymmetrical collections of molecules inside stem cells,' Dr González says. 'This suggests new lines of investigation into the relationship between stem cells and tumours in other model organisms and humans.' To download the abstract of the Nature Genetics article, please visit the following website: http://www.nature.com/ng/index.html Remarks: Reference document: E. Caussinus and C. González. Induction of tumour growth by altered stem-cell asymmetric division in Drosophila melanogaster. Nature Genetics, 4 September 2005