16/01/2017
Medulloblastoma, the tumor of the cerebellum, is the most common childhood brain tumor, and despite the acceptable rate of survival, the toxicity of the treatments currently in use and in particular the radiation therapy cause serious damage in patients, including permanent cognitive disorders and secondary malignancies.
A group of researchers of the Institute of Cell Biology and Neurobiology of the CNR (National Research Council-IBCN) - by exploiting the experience born from a decade of studies on the development of neurons (neurogenesis) in the brain and cerebellum, has demonstrated in vivo that after treatment with the Cxcl3 protein, when the tumor has already started to develop, the medulloblastoma disappears completely. The study is published in Frontiers in Pharmacology.
"Already in 2012 we had identified the chemokine Cxcl3 as a possible therapeutic target, demonstrating that the lack of this protein leads to a substantial increase in the frequency of medulloblastoma, since the cerebellar precursors - that is, the young cells which then become neurons – are no longer able to migrate out of the proliferative zone to the surface of the cerebellum and therefore tend to become neoplastic. In fact, a longer stay in the proliferative area makes the precursor cells more susceptible to mutations that trigger an uncontrolled proliferation" explains Felice Tirone of Ibcn-CNR, who led the research in collaboration with Manuela Ceccarelli and Laura Micheli. "Using this information, we have now shown that if a mouse model that develops medulloblastoma with high frequency is treated for a month in the cerebellum with Cxcl3, until the age of two months, that is, when the tumor has already started to grow, then the medulloblastoma does not develop and disappears completely. "
The peculiarity of this study is the procedure totally different from those in use, which are essentially based on blocking the proliferation of cerebellar cancer precursor cells by toxic substances. "Our approach instead exploits the residual plasticity of the cerebellar neoplastic precursor cells, since Cxcl3 forces them to migrate outside of the proliferative zone of the cerebellum toward the inner regions, where the neoplastic precursor cells differentiate, thus exiting definitively from the tumor program", states the researcher.
The applicability of this treatment in humans, which has been patented by the Cnr (Cxcl3 chemokine for the therapeutic treatment of medulloblastoma, Patent WO 2014053999 A1), is now under study. "Cxcl3 seems to be non-toxic even at high doses, but it remains unclear whether the plasticity of cerebellar tumor precursor cells, that is the ability to differentiate after migration, remains at more advanced stages of the cancer," says Tirone. "One possible application would be in Gorlin syndrome, where the medulloblastoma is transmitted genetically (frequency 1: 50.000), and therefore its onset is more predictable and can be monitored at an early stage of development."
This research was funded with a grant from the Italian Foundation for Research on Cancer assigned to Manuela Ceccarelli in 2014 and the project FareBio of the Ministry of Economy and Finance awarded to Felice Tirone.
Rome, 16 January 2017
Data summary:
What: Using chemokine Cxcl3 for a potential new treatment of medulloblastoma.
Ceccarelli M, Micheli L and Tirone F (2016). Suppression of medulloblastoma lesions by forced migration of precursor cells with preneoplastic intracerebellar administration of the chemokine Cxcl3. Front. Pharmacol. 7: 484. doi: 10.3389 / fphar.2016.00484
Who: Institute of Cell Biology and Neurobiology of the National Research Council (Ibcn-Cnr)
For information: Felice Tirone, Ibcn-Cnr, tel.0039-06.50170-3184, e-mail: felice.tirone@cnr.it
Press Office Cnr: Rita Bugliosi, tel. 06/49932021, -3383, e-mail: rita.bugliosi@cnr.it
Per informazioni:
Felice Tirone
Ibcn-Cnr
felice.tirone@cnr.it
Ufficio stampa:
Rita Bugliosi
Ufficio stampa Cnr
rita.bugliosi@cnr.it
Responsabile Unità Ufficio stampa:
Marco Ferrazzoli
marco.ferrazzoli@cnr.it
ufficiostampa@cnr.it
06 4993 3383