A team of researchers at the Gulbenkian Science Institute (IGC) has decoded a genetic program that controls the dissemination of glioblastoma cells (a malignant brain tumor), the institute announced today.
Of all adult brain tumors, glioblastoma, with an estimated prevalence rate of 1 in 100,000, is the "most frequent and the one with the worst prognosis," due to the tumor's ability to invade the surrounding brain tissue, making its surgical removal "extremely difficult," and it can even "invariably reappear after surgery," the IGC statement explains.
According to the institute, this reappearance is due to the fact that "the cancerous cells easily mix with the surrounding tissue's normal cells, making it difficult for the surgeon to remove the whole tumor." Furthermore, glioblastoma contains the tumor's so-called 'stem' cells - that is, they have the ability to generate a new tumor, especially when they are 'left behind'.
"The invasiveness of this tumor type is such a serious matter that many researchers are trying to understand the mechanisms that enable glioblastoma cells to invade the brain tissue around them," says Diogo Castro, the researcher who led the team that conducted the study, quoted on an IGC statement.
Zeb1 is the name of a molecule known to be involved in the glioblastoma invasion process. According to Pedro Rosmaninho, the first author of this study and one of the researchers in Diogo Castro's group, "Zeb1 belongs to an important group of regulatory molecules called 'transcription factors'. They operate within cells much in the same way as a maestro conducts his orchestra, telling the musicians when to start or stop playing. 'Transcription factors' do the same thing with genes".
In the aforementioned statement, the IGC researcher says that this finding has revealed the way Zeb1 "plays its role within cancer cells when it enables them to invade healthy brain tissues around them," thereby confirming the molecule's crucial role in glioblastoma.
The researchers used cell cultures created from human biopsies and databases containing the genetic profile of hundreds of glioblastoma tumors in order to map Zeb1-regulated genes in the human genome.
The experiment has shown that "the molecule orchestrates important changes in the properties of cancer cells, playing a double role - that is, its presence can simultaneously 'turn on' or 'turn off' a large number of genes." This ends up changing the way cancer cells interact, which are then able to infiltrate the brain tissue where the tumor grows.
In today's statement, Diogo Castro stresses the importance of this study: "The better we understand the way glioblastoma tumor cells invade the surrounding brain tissues, the closer we will be to finding effective therapies which can disrupt this process."
The study was conducted at the Gulbenkian Science Institute in collaboration with researchers from the Edinger Institute of Neurology (Germany) and McGill University (Canada) and was funded by the Foundation for Science and Technology (FCT), the Deutsche Forschungsgemeinschaft (Germany) and the Canadian Institute of Health (Canada).