Link Found Between Stem Cells and Tumors

Researchers now have proof that certain kinds of cancer originates with stem cell defects. A recent study demonstrates that if key molecules are not positioned in the proper locations within stem cells before they divide, the result can be deadly tumor formation.

Cells in the very early embryo are identical and undergo fast division. However, they soon begin differentiating into more specific types, eventually becoming specialized cells such as blood, neurons, or muscle. As they differentiate, they should stop dividing and usually become entrenched in specific tissues. Some tumor cells are more like stem cells because they are identical, they divide rapidly, and in the worst case--metastasis--they travel through the body and implant themselves in new tissues.

Specialized cells die by way of age or injuries, so the body keeps reserves of stem cells on hand to produce replacements. Typically, the stem cell divides into two types: one that is just like the parent, which is kept to maintain the stock, and another that differentiates. This is what occurs 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 occur before division. The parent cell becomes asymmetrical: it accumulates a set of special molecules, including Prospero and other proteins, in the region that will sprout off and become the specialized cell.

This research was performed by investigators from the European Molecular Biology Laboratory (EMBL, Heidelberg, Germany) and the Institute of Biomedical Research of the Parc Cientific de Barcelona (IRB-PCB; Spain). Their findings were published in the September 4, 2005, on-line edition of the journal Nature Genetics.

"This asymmetry provides the new cell with molecules it needs to launch new genetic programs that tell it what to become,” remarked Dr. Cayetano Gonzalez, whose team started the project at EMBL and has continued to study the process as they moved to the IRB-PCB. "The current study investigates what happens when the process of localizing these molecules is disturbed.”

Whether Prospero and its cohorts get to the proper place depends on the activity of specific genes in the stem cell. Emmanuel Caussinus, an EMBL Ph.D. student from Dr. González's group, created neuroblasts in which these genes were disrupted. "We no longer had normal neuroblasts and daughter cells capable of becoming part of a nerve,” Mr. Caussinus noted. "Instead, we had a tumor.”

When these modified cells were transplanted into flies, the results were quick and dramatic. The tissue containing the modified cells grew to 100 times its initial size, cells invaded other tissues, and death followed. The growing tumor became "immortal,” according to Mr. Caussinus. Cells could be re-transplanted into new hosts for years, generation after generation, with similar effects.

This study confirms that certain genes in stem cells--those which regulate the destinies of daughter cells--are vital. 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,” said Dr. González. "This suggests new lines of investigation into the relationship between stem cells and tumors in other model organisms and humans.”


Related Links:
European Molecular Biology Laboratory
Parc Cientific de Barcelona