Two types of cells triggering brain tumors have been identified

José Pichel Andrés/ DICYT A study proved the existence of two types of tumor stem cells producing glioblastomas, the most aggressive brain tumors. On one hand, a type of cancer-triggering cells are in the tumor mass; on the other, another group of cells with greater mobility placed on tumors spreads and, as these cells cannot be removed by surgery, recurrences occur. This finding has been published in Stem Cells and it is considered the first step to develop therapies preventing cancer recurrence.

For some time now, experts have been observing the existence of cancer-initiating cells behaving just like stem cells: producing other tumor cells. The major objective of this study was to determine whether all these initiating-cells were equal in glioblastoma multiforme (Gliobastoma-Initianing Cells, GICs); scientists found two very different groups, as DiCYT was told by Atanasio Pandiella, assistant manager at the Centro de Investigación del Cáncer (CIC) –a cancer research center in Salamanca (Spain)-, and a member of the team carrying out this research at the Hospital Universitario de Valdecilla (Cantabria, Spain).

“We have analyzed the central area and the surface of tumors, and initiating-cells have been isolated from tumor mass in both areas, proving to have different properties,” Pandiella states. Cells on the tumor are more aggressive, migrate and move better. This data, hitherto unknown, explains the reason why in glioblastomas recurrences may occur; as brain is such a delicate tissue, surgeons only remove the central tumor mass. Nevertheless, border GICs easily scatter towards other healthy parts of the brain and may repeat the problem quickly.

“We are unable to detect them, but they move towards areas around, so when a tumor is removed, some of them had already moved and recurrence happens”, the expert states. Stem cells in the tumors are more proliferate, but do not move a lot, so they are a minor problem compared to outer cells starting the disease again.

Differentiating Features

“We have studied the features of both types of cells and we found cells on tumors have mechanisms allowing them to move efficiently,” the researcher explains.

Rac proteins are elements associated with those mechanisms, involved in cell migration and, in this case, they are much more active in border GICs. Moreover, there is another important protein to make the difference between the two types of cells: protein p27, a tumor suppressor (when its levels raise, cells do not divide). Protein p27 is very active in cells inside tumors, whereas “in initiating-cells on tumors, it is less common; this stimulates proliferation and mobility”.

Researchers have also understood the importance of some cell membrane proteins called integrins, involved in interactions with neighbor cells and sometimes they are essential for displacements.
For the time being, for instance, there aren’t drugs able to inhibit Rac and to make p27 proliferate, but understanding these mechanisms is the first step towards a therapy preventing, or at least reducing, gliobastoma relapses.

These findings have their origin in an extensive collaborative work by several centers focused on samples from three patients. Additionally, in vitro experiments and animal tests have been carried out to corroborate results and to understand the behavior of these molecules.

Developing Therapies

Their next step would be to develop therapies against tumor-initiating cells on glioblastoma. “Understanding dissemination mechanisms is a way to fight them”, Pandiella says. “We are trying to kill these cells, or at least stop their proliferation and movement”. As a lesser evil, while surgery is required to uproot tumors, scientists expect to better understand the area to be removed”.

Some cancers, such as breast or lung cancer, are lethal when metastasis occurs in the brain, but in this case, “cancer is already in the brain”, the expert explains underlying the severity of gliobastoma, the most aggressive glioma or brain tumor, so studies of this kind must be continued.

References

Ruiz-Ontañon P, Orgaz JL, Aldaz B, Elosegui-Artola A, Martino J, Berciano MT, Montero JA, Grande L, Nogueira L, Diaz-Moralli S, Esparís-Ogando A, Vazquez-Barquero A, Lafarga M, Pandiella A, Cascante M, Segura V, Martinez-Climent JA, Sanz-Moreno V, Fernandez-Luna JL. Cellular Plasticity Confers Migratory and Invasive Advantages to a Population of Glioblastoma-initiating Cells that Infiltrate Peritumoral Tissue. Stem Cells. 2013 Feb 8. doi: 10.1002/stem.1349