A research team, with the participation of the University of Granada, has proven that two small structural elements, called decorin and lumican, could be decisive in the development of a resistance to the drugs currently used for treating glioblastoma multiforme, such as temozolamide.
It’s the most frequent and aggressive tumor that affects the central nervous system, and it has a low survival rate: less than a year and a half after being diagnosed.
A research team, with the participation of the University of Granada (UGR), has made some progress indetermining the causes for glioblastoma multiforme (GBM), one of the mostaggressive brain tumors known, to be resistant to the drugs currently used,which is one of the main limitations of its treatment. The results have beenrecently published in two articles in PlosOne magazine.
The researchers have proven that proteoglycans(the cells’ structural elements), called decorin (DCN) and lumican (LUM), couldbe decisive in the behavior and development of a resistance to the drugs usedfor treating glioblastoma multiforme, such as temozolamide (TMZ). In the otherhand, they have laid bare that the inhibition of the transcription of some of thesub-units belonging to the mismatch-repair (MMR) complex, a system thatanalyzes and repairs DNA, could be responsible of the failure of currenttherapies against this kind of tumor.
This is a scientific breakthrough that could beuseful for the search of new resistance markers in GBM as well as for thedevelopment of new therapeutic strategies which avoid the resistance to drugsthat this tumors possess.
The researches on glioblastoma stem-like cellshave been carried out by researchers from the UGR Institute of Biopathology andRegenerative Medicine (Instituto de Biopatología y Medicina Regenerativa,IBIMER) and from the Biosanitary Institute of Granada (group CTS 107), incollaboration with the Bellvitge Biomedical Research Institute (Barcelona) andthe Service of Medical Oncology (Granada) in the one hand, and the NationalInstitute of Biostructures and Biosystems (Istituto Nazionale Biostrutture eBiosistemi, INBB, Rome) and the department of Biomedical Sciences(University of Sassari, Rome) in the other hand.
Low survival rate
GBMs, the most frequent and most aggressivetumors that affect the central nervous system, still present a low survivalrate (less than a year and a half since its diagnosis), despite the use of TMZcombined with other drugs or with radiotherapy. This is due to, among othercauses, the development of a resistance to the treatment.
This work analyzes how the massive, synergisticexpression of DCN and LUM in neurospheres of stem-like cells derived from GBMis correlated with a lower tumor cells proliferation rate and with a lowerdevelopment of apoptosis (a type of cellular death used by pluricellularorganisms to eliminate damaged or unnecessary cells), but also its correlationwith the rise in the resistance against TMZ treatments, which is one of themain drugs currently used in the treatment of this patients.
In the other hand, researches carried out inglioblastoma and neuroblastoma cell lines exposed to some drugs have proventhat TMZ resistance is caused not only by the classic mechanism of theDNA-repairing enzyme MGMT, but it’s also related with the silencing of the MMRcomplex after the exposure to the drug.
The researches are now focused on proving therelevance of these two molecules in the ‘in vivo’ behavior ofglioblastomas and analyzing the resistance mechanism based in the MMR complex.
Bibliographic references:
Perazzoli G. et al. (2015) TemozolomideResistance in Glioblastoma Cell Lines: Implication of MGMT, MMR, P-Glycoproteinand CD133 Expression. PLoS ONE 10(10): e0140131. doi:10.1371/journal.pone.0140131
Farace C. et al. (2015) MicroenvironmentalModulation of Decorin and Lumican in Temozolomide-Resistant Glioblastoma andNeuroblastoma Cancer Stem-Like Cells.
PLoSONE 10(7):e0134111.doi: 10.1371/journal.pone.0134111.
Links to complete articles:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4598115/
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4521885/
Contact:
José Carlos Prados Salazar
Professor at ‘Departamento de Anatomía yEmbriología Humana. Instituto de Biopatología y Medicina Regenerativa’, University of Granada.
Telephone: (+34) 958 248 819 | (+34) 958 241000 ext. 20015/20032
E-mail: jcprados@ugr.es
